{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T22:04:36Z","timestamp":1790546676233,"version":"4.1.0"},"reference-count":132,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2021,11,12]],"date-time":"2021-11-12T00:00:00Z","timestamp":1636675200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The primary cilium is found in most mammalian cells and plays a functional role in tissue homeostasis and organ development by modulating key signaling pathways. Ciliopathies are a group of genetically heterogeneous disorders resulting from defects in cilia development and function. Patients with ciliopathic disorders exhibit a range of phenotypes that include nephronophthisis (NPHP), a progressive tubulointerstitial kidney disease that commonly results in end-stage renal disease (ESRD). In recent years, distal appendages (DAPs), which radially project from the distal end of the mother centriole, have been shown to play a vital role in primary ciliary vesicle docking and the initiation of ciliogenesis. Mutations in the genes encoding these proteins can result in either a complete loss of the primary cilium, abnormal ciliary formation, or defective ciliary signaling. DAPs deficiency in humans or mice commonly results in NPHP. In this review, we outline recent advances in our understanding of the molecular functions of DAPs and how they participate in nephronophthisis development.<\/jats:p>","DOI":"10.3390\/ijms222212253","type":"journal-article","created":{"date-parts":[[2021,11,14]],"date-time":"2021-11-14T20:48:36Z","timestamp":1636922916000},"page":"12253","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["The Role of Centrosome Distal Appendage Proteins (DAPs) in Nephronophthisis and Ciliogenesis"],"prefix":"10.3390","volume":"22","author":[{"given":"Fatma","family":"Mansour","sequence":"first","affiliation":[{"name":"Department of Nephrology and Medical Intensive Care, Charit\u00e9-Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"},{"name":"Molecular and Translational Kidney Research, Max-Delbr\u00fcck-Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany"},{"name":"Department of Pathology, Faculty of Veterinary Medicine, Cairo University, 12613 Giza, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix J.","family":"Boivin","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Medical Intensive Care, Charit\u00e9-Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"},{"name":"Molecular and Translational Kidney Research, Max-Delbr\u00fcck-Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iman B.","family":"Shaheed","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Veterinary Medicine, Cairo University, 12613 Giza, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Schueler","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Medical Intensive Care, Charit\u00e9-Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7700-7142","authenticated-orcid":false,"given":"Kai M.","family":"Schmidt-Ott","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Medical Intensive Care, Charit\u00e9-Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"},{"name":"Molecular and Translational Kidney Research, Max-Delbr\u00fcck-Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.gde.2019.05.002","article-title":"Cilia and development","volume":"56","author":"Sreekumar","year":"2019","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/s41581-019-0116-9","article-title":"Cellular signalling by primary cilia in development, organ function and disease","volume":"15","author":"Anvarian","year":"2019","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"F1159","DOI":"10.1152\/ajprenal.00118.2005","article-title":"An incredible decade for the primary cilium: A look at a once-forgotten organelle","volume":"289","author":"Davenport","year":"2005","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5519","DOI":"10.1073\/pnas.90.12.5519","article-title":"A motility in the eukaryotic flagellum unrelated to flagellar beating","volume":"90","author":"Kozminski","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1083\/jcb.151.3.709","article-title":"Chlamydomonas IFT88 and its mouse homologue, polycystic kidney disease gene tg737, are required for assembly of cilia and flagella","volume":"151","author":"Pazour","year":"2000","journal-title":"J. Cell Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.cell.2016.11.036","article-title":"An actin network dispatches ciliary GPCRs into extracellular vesicles to modulate signaling","volume":"168","author":"Nager","year":"2017","journal-title":"Cell"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Labour, M.-N., Riffault, M., Christensen, S.T., and Hoey, D.A. (2016). TGF\u03b21\u2013induced recruitment of human bone mesenchymal stem cells is mediated by the primary cilium in a SMAD3-dependent manner. Sci. Rep., 6.","DOI":"10.1038\/srep35542"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"a028167","DOI":"10.1101\/cshperspect.a028167","article-title":"Primary cilia and coordination of receptor tyrosine kinase (RTK) and transforming growth factor \u03b2 (TGF-\u03b2) signaling","volume":"9","author":"Christensen","year":"2017","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"8","DOI":"10.3389\/fcell.2018.00008","article-title":"Signaling through the primary cilium","volume":"6","author":"Wheway","year":"2018","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Haycraft, C.J., Banizs, B., Aydin-Son, Y., Zhang, Q., Michaud, E.J., and Yoder, B.K. (2005). Gli2 and Gli3 localize to cilia and require the intraflagellar transport protein polaris for processing and function. PLoS Genet., 1.","DOI":"10.1371\/journal.pgen.0010053"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Pala, R., Alomari, N., and Nauli, S.M. (2017). Primary Cilium-Dependent Signaling Mechanisms. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18112272"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1002\/path.3004","article-title":"Primary cilia and coordination of receptor tyrosine kinase (RTK) signalling","volume":"226","author":"Christensen","year":"2012","journal-title":"J. Pathol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1016\/j.cub.2005.09.012","article-title":"PDGFRalphaalpha signaling is regulated through the primary cilium in fibroblasts","volume":"15","author":"Schneider","year":"2005","journal-title":"Curr. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1038\/nrg3272","article-title":"The Notch signalling system: Recent insights into the complexity of a conserved pathway","volume":"13","author":"Guruharsha","year":"2012","journal-title":"Nat. Reviews Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1101\/gad.207043.112","article-title":"Centriole distal appendages promote membrane docking, leading to cilia initiation","volume":"27","author":"Tanos","year":"2013","journal-title":"Genes Dev."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Yang, T.T., Chong, W.M., Wang, W.J., Mazo, G., Tanos, B., Chen, Z., and Liao, J.C. (2018). Super-resolution architecture of mammalian centriole distal appendages reveals distinct blade and matrix functional components. Nat. Commun., 9.","DOI":"10.1038\/s41467-018-04469-1"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1038\/s41467-018-08216-4","article-title":"High-resolution characterization of centriole distal appendage morphology and dynamics by correlative STORM and electron microscopy","volume":"10","author":"Bowler","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"jcs223594","DOI":"10.1242\/jcs.223594","article-title":"LRRC45 contributes to early steps of axoneme extension","volume":"131","author":"Kurtulmus","year":"2018","journal-title":"J. Cell Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1038\/ng.2007.80","article-title":"Mutations in pericentrin cause Seckel syndrome with defective ATR-dependent DNA damage signaling","volume":"40","author":"Griffith","year":"2008","journal-title":"Nat. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/ng.725","article-title":"CEP152 is a genome maintenance protein disrupted in Seckel syndrome","volume":"43","author":"Kalay","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1126\/science.1151174","article-title":"Mutations in the pericentrin (PCNT) gene cause primordial dwarfism","volume":"319","author":"Rauch","year":"2008","journal-title":"Science"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1053\/j.ajkd.2020.08.012","article-title":"Ciliopathies and the Kidney: A Review","volume":"77","author":"McConnachie","year":"2021","journal-title":"Am. J. Kidney Dis. Off. J. Natl. Kidney Found."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1056\/NEJMra1010172","article-title":"Ciliopathies","volume":"364","author":"Hildebrandt","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1038\/s41556-018-0132-1","article-title":"Differential regulation of transition zone and centriole proteins contributes to ciliary base diversity","volume":"20","author":"Jana","year":"2018","journal-title":"Nat. Cell Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"243","DOI":"10.14348\/molcells.2017.0054","article-title":"The ciliary transition zone: Finding the pieces and assembling the gate","volume":"40","author":"Pelletier","year":"2017","journal-title":"Mol. Cells"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1038\/nrm.2017.60","article-title":"Genes and molecular pathways underpinning ciliopathies","volume":"18","author":"Reiter","year":"2017","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"a028233","DOI":"10.1101\/cshperspect.a028233","article-title":"Multiciliated cells in animals","volume":"8","author":"Meunier","year":"2016","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1016\/S0960-9822(01)00484-5","article-title":"Localization of intraflagellar transport protein IFT52 identifies basal body transitional fibers as the docking site for IFT particles","volume":"11","author":"Deane","year":"2001","journal-title":"Curr. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Joukov, V., and De Nicolo, A. (2019). The centrosome and the primary cilium: The Yin and Yang of a hybrid organelle. Cells, 8.","DOI":"10.3390\/cells8070701"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.jbior.2016.09.002","article-title":"Rab11 and phosphoinositides: A synergy of signal transducers in the control of vesicular trafficking","volume":"63","author":"Campa","year":"2017","journal-title":"Adv. Biol. Regul."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1016\/j.febslet.2015.05.001","article-title":"PI3K-C2\u03b1: One enzyme for two products coupling vesicle trafficking and signal transduction","volume":"589","author":"Campa","year":"2015","journal-title":"FEBS Lett."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/S0070-2153(08)00802-8","article-title":"Intraflagellar transport (IFT) role in ciliary assembly, resorption and signalling","volume":"85","author":"Pedersen","year":"2008","journal-title":"Curr. Top. Dev. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"a028092","DOI":"10.1101\/cshperspect.a028092","article-title":"The intraflagellar transport machinery","volume":"8","author":"Taschner","year":"2016","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2905","DOI":"10.1111\/febs.14068","article-title":"Intraflagellar transport: Mechanisms of motor action, cooperation, and cargo delivery","volume":"284","author":"Prevo","year":"2017","journal-title":"FEBS J."},{"key":"ref_35","first-page":"E2841","article-title":"CEP164 triggers ciliogenesis by recruiting Tau tubulin kinase 2 to the mother centriole","volume":"111","author":"Nigg","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/j.ajhg.2014.05.002","article-title":"Mutations of CEP83 cause infantile nephronophthisis and intellectual disability","volume":"94","author":"Failler","year":"2014","journal-title":"Am. J. Hum. Genet."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Katagiri, S., Hayashi, T., Yoshitake, K., Murai, N., Matsui, Z., Kubo, H., Satoh, H., Matsufuji, S., Takamura, T., and Yokoo, T. (2018). Compound heterozygous splice site variants in the SCLT1 gene highlight an additional candidate locus for Senior-L\u00f8ken syndrome. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-35152-6"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2949","DOI":"10.1093\/hmg\/ddx183","article-title":"SCLT1 deficiency causes cystic kidney by activating ERK and STAT3 signaling","volume":"26","author":"Li","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Slaats, G.G. (2014). Nephronophthisis-associated CEP164 regulates cell cycle progression, apoptosis and epithelial-to-mesenchymal transition. PLoS Genet., 10.","DOI":"10.1371\/journal.pgen.1004594"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.kint.2019.04.014","article-title":"Roscovitine blocks collecting duct cyst growth in CEP164-deficient kidneys","volume":"96","author":"Airik","year":"2019","journal-title":"Kidney Int."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2204","DOI":"10.1002\/ajmg.a.62225","article-title":"Beyond nephronophthisis: Retinal dystrophy in the absence of kidney dysfunction in childhood expands the clinical spectrum of CEP83 deficiency","volume":"185","author":"Veldman","year":"2021","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e202011133","DOI":"10.1083\/jcb.202011133","article-title":"A ciliopathy complex builds distal appendages to initiate ciliogenesis","volume":"220","author":"Kumar","year":"2021","journal-title":"J. Cell Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1038\/nrm2278","article-title":"When cilia go bad: Cilia defects and ciliopathies","volume":"8","author":"Fliegauf","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2333","DOI":"10.1007\/s00467-008-0840-z","article-title":"Nephronophthisis","volume":"24","author":"Salomon","year":"2009","journal-title":"Pediatric Nephrol."},{"key":"ref_45","unstructured":"Stokman, M., Lilien, M., and Knoers, N. (2016). Nephronophthisis. GeneReviews\u00ae Internet, University of Washington."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4131","DOI":"10.1242\/dev.02595","article-title":"The roles of cilia in developmental disorders and disease","volume":"133","author":"Bisgrove","year":"2006","journal-title":"Development"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1681\/ASN.2008050456","article-title":"Nephronophthisis: Disease Mechanisms of a Ciliopathy","volume":"20","author":"Hildebrandt","year":"2009","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"287","DOI":"10.3389\/fped.2017.00287","article-title":"Many genes\u2014one disease? Genetics of Nephronophthisis (NPHP) and NPHP-associated disorders","volume":"5","author":"Srivastava","year":"2018","journal-title":"Front. Pediatrics"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1111\/nep.13393","article-title":"Nephronophthisis: A review of genotype\u2013phenotype correlation","volume":"23","author":"Luo","year":"2018","journal-title":"Nephrology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1772","DOI":"10.1681\/ASN.2017111200","article-title":"NPHP1 (Nephrocystin-1) Gene Deletions Cause Adult-Onset ESRD","volume":"29","author":"Snoek","year":"2018","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/s00467-010-1585-z","article-title":"Nephronophthisis","volume":"26","author":"Wolf","year":"2011","journal-title":"Pediatric Nephrol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1002\/ajmg.a.36501","article-title":"Arts. Early presentation of cystic kidneys in a family with a homozygous INVS mutation","volume":"164","author":"Oud","year":"2014","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1681\/ASN.2006121344","article-title":"Nephronophthisis-associated ciliopathies","volume":"18","author":"Hildebrandt","year":"2007","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1148\/rg.341135179","article-title":"From the Radiologic Pathology Archives: Pediatric Polycystic Kidney Disease and Other Ciliopathies: Radiologic-Pathologic Correlation","volume":"34","author":"Chung","year":"2014","journal-title":"RadioGraphics"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1038\/ng1520","article-title":"Nephrocystin-5, a ciliary IQ domain protein, is mutated in Senior-Loken syndrome and interacts with RPGR and calmodulin","volume":"37","author":"Otto","year":"2005","journal-title":"Nat. Genet."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"a028191","DOI":"10.1101\/cshperspect.a028191","article-title":"Ciliopathies","volume":"9","author":"Braun","year":"2017","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.visres.2012.07.003","article-title":"Senior-L\u00f8ken syndrome: A syndromic form of retinal dystrophy associated with nephronophthisis","volume":"75","author":"Ronquillo","year":"2012","journal-title":"Vis. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1111\/j.1469-8749.2011.04021.x","article-title":"The ciliopathies in neuronal development: A clinical approach to investigation of Joubert syndrome and Joubert syndrome-related disorders","volume":"53","author":"Sattar","year":"2011","journal-title":"Dev. Med. Child Neurol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"R235","DOI":"10.1093\/hmg\/ddi264","article-title":"Genetic basis of Joubert syndrome and related disorders of cerebellar development","volume":"15","author":"Louie","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1136\/jmg.2007.052027","article-title":"Mutation analysis of NPHP6\/CEP290 in patients with Joubert syndrome and Senior\u2013L\u00f8ken syndrome","volume":"44","author":"Helou","year":"2007","journal-title":"J. Med Genet."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"244","DOI":"10.3389\/fped.2017.00244","article-title":"Meckel-Gruber Syndrome: An Update on Diagnosis, Clinical Management, and Research Advances","volume":"5","author":"Hartill","year":"2017","journal-title":"Front. Pediatrics"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1159\/000331268","article-title":"Mutations in SDCCAG8\/NPHP10 Cause Bardet-Biedl Syndrome and Are Associated with Penetrant Renal Disease and Absent Polydactyly","volume":"1","author":"Schaefer","year":"2011","journal-title":"Mol. Syndr."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1007\/s00467-007-0435-0","article-title":"Bardet-Biedl syndrome: Beyond the cilium","volume":"22","author":"Tobin","year":"2007","journal-title":"Pediatric Nephrol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.cell.2011.04.019","article-title":"Mapping the NPHP-JBTS-MKS protein network reveals ciliopathy disease genes and pathways","volume":"145","author":"Sang","year":"2011","journal-title":"Cell"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1016\/j.cell.2015.10.065","article-title":"A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface","volume":"163","author":"Gupta","year":"2015","journal-title":"Cell"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1083\/jcb.201009069","article-title":"NPHP4, a cilia-associated protein, negatively regulates the Hippo pathway","volume":"193","author":"Habbig","year":"2011","journal-title":"J. Cell Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1038\/ng.891","article-title":"A transition zone complex regulates mammalian ciliogenesis and ciliary membrane composition","volume":"43","author":"Corbit","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1091\/mbc.E19-09-0499","article-title":"Novel fibrillar structure in the inversin compartment of primary cilia revealed by 3D single-molecule superresolution microscopy","volume":"31","author":"Bennett","year":"2020","journal-title":"Mol. Biol. Cell"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1038\/ng1217","article-title":"Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determination","volume":"34","author":"Otto","year":"2003","journal-title":"Nat. Genet."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"135","DOI":"10.5414\/CNP69135","article-title":"Association of INVS (NPHP2) mutation in an adolescent exhibiting nephronophthisis (NPH) and complete situs inversus","volume":"69","author":"Okada","year":"2008","journal-title":"Clin. Nephrol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1038\/ki.2008.662","article-title":"Mutations of NPHP2 and NPHP3 in infantile nephronophthisis","volume":"75","author":"Tory","year":"2009","journal-title":"Kidney Int."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"4097","DOI":"10.1093\/ndt\/gfq519","article-title":"A homozygous mutation in INVS causing juvenile nephronophthisis with abnormal reactivity of the Wnt\/beta-catenin pathway","volume":"25","author":"Bellavia","year":"2010","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3389\/fped.2018.00175","article-title":"Congenital Heart Defects and Ciliopathies Associated With Renal Phenotypes","volume":"6","author":"Gabriel","year":"2018","journal-title":"Front. Pediatrics"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"6023","DOI":"10.1038\/ncomms7023","article-title":"ANKS6 is the critical activator of NEK8 kinase in embryonic situs determination and organ patterning","volume":"6","author":"Czarnecki","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2537","DOI":"10.15252\/embj.201488044","article-title":"Formation of the transition zone by Mks5\/Rpgrip1L establishes a ciliary zone of exclusion (CIZE) that compartmentalises ciliary signalling proteins and controls PIP2 ciliary abundance","volume":"34","author":"Jensen","year":"2015","journal-title":"EMBO J."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1091\/mbc.E20-03-0190","article-title":"Rpgrip1l controls ciliary gating by ensuring the proper amount of CEP290 at the vertebrate transition zone","volume":"32","author":"Wiegering","year":"2021","journal-title":"Mol. Biol. Cell"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1083\/jcb.201408060","article-title":"The transition zone protein Rpgrip1l regulates proteasomal activity at the primary cilium","volume":"210","author":"Gerhardt","year":"2015","journal-title":"J. Cell Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.1242\/dev.003715","article-title":"Ftm is a novel basal body protein of cilia involved in Shh signalling","volume":"134","author":"Vierkotten","year":"2007","journal-title":"Development"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1080\/15548627.2018.1429874","article-title":"The ciliary protein RPGRIP1L governs autophagy independently of its proteasome-regulating function at the ciliary base in mouse embryonic fibroblasts","volume":"14","author":"Struchtrup","year":"2018","journal-title":"Autophagy"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1038\/ng2039","article-title":"The ciliary gene RPGRIP1L is mutated in cerebello-oculo-renal syndrome (Joubert syndrome type B) and Meckel syndrome","volume":"39","author":"Delous","year":"2007","journal-title":"Nat. Genet."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1002\/humu.21337","article-title":"CEP290, a gene with many faces: Mutation overview and presentation of CEP290base","volume":"31","author":"Coppieters","year":"2010","journal-title":"Hum. Mutat."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1007\/978-1-4614-3209-8_66","article-title":"CEP290 and the primary cilium","volume":"801","author":"Drivas","year":"2014","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"4565","DOI":"10.1093\/hmg\/ddp422","article-title":"A mouse model for Meckel syndrome reveals Mks1 is required for ciliogenesis and Hedgehog signaling","volume":"18","author":"Weatherbee","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/ng1714","article-title":"MKS1, encoding a component of the flagellar apparatus basal body proteome, is mutated in Meckel syndrome","volume":"38","author":"Tallila","year":"2006","journal-title":"Nat. Genet."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2058","DOI":"10.1158\/0008-5472.CAN-07-5838","article-title":"Cell cycle-dependent ciliogenesis and cancer","volume":"68","author":"Plotnikova","year":"2008","journal-title":"Cancer Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1038\/ncb3370","article-title":"Cilium assembly and disassembly","volume":"18","author":"Dynlacht","year":"2016","journal-title":"Nat. Cell Biol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.1042\/BCJ20170453","article-title":"Cilium structure, assembly, and disassembly regulated by the cytoskeleton","volume":"475","author":"Mirvis","year":"2018","journal-title":"Biochem. J."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1038\/ncb3109","article-title":"Early steps in primary cilium assembly require EHD1\/EHD3-dependent ciliary vesicle formation","volume":"17","author":"Lu","year":"2015","journal-title":"Nat. Cell Biol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/j.devcel.2015.03.012","article-title":"Ciliary vesicle formation: A prelude to ciliogenesis","volume":"32","author":"Yee","year":"2015","journal-title":"Dev. Cell"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"6346","DOI":"10.1073\/pnas.1002401107","article-title":"Coordination of Rab8 and Rab11 in primary ciliogenesis","volume":"107","author":"Feng","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2759","DOI":"10.1073\/pnas.1018823108","article-title":"Primary cilia membrane assembly is initiated by Rab11 and transport protein particle II (TRAPPII) complex-dependent trafficking of Rabin8 to the centrosome","volume":"108","author":"Westlake","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1111\/boc.201800074","article-title":"Ciliary kinesins beyond IFT: Cilium length, disassembly, cargo transport and signalling","volume":"111","author":"Reilly","year":"2019","journal-title":"Biol. Cell"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1242\/jcs.077156","article-title":"Centriolar satellites are assembly points for proteins implicated in human ciliopathies, including oral-facial-digital syndrome 1","volume":"124","author":"Lopes","year":"2011","journal-title":"J. Cell Sci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1091\/mbc.e13-09-0526","article-title":"The novel centriolar satellite protein SSX2IP targets Cep290 to the ciliary transition zone","volume":"25","author":"Klinger","year":"2014","journal-title":"Mol. Biol. Cell"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1242\/jcs.179713","article-title":"WDR8 is a centriolar satellite and centriole-associated protein that promotes ciliary vesicle docking during ciliogenesis","volume":"129","author":"Kurtulmus","year":"2016","journal-title":"J. Cell Sci."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/s41586-020-2139-6","article-title":"Centrosome anchoring regulates progenitor properties and cortical formation","volume":"580","author":"Shao","year":"2020","journal-title":"Nature"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"3489","DOI":"10.1083\/jcb.201811142","article-title":"Phosphorylation of CEP83 by TTBK2 is necessary for cilia initiation","volume":"218","author":"Lo","year":"2019","journal-title":"J. Cell Biol."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Huang, H. (2018). Matrix metalloproteinase-9 (MMP-9) as a cancer biomarker and MMP-9 biosensors: Recent advances. Sensors, 18.","DOI":"10.3390\/s18103249"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"4511","DOI":"10.1038\/s41467-018-06990-9","article-title":"M-Phase Phosphoprotein 9 regulates ciliogenesis by modulating CP110-CEP97 complex localization at the mother centriole","volume":"9","author":"Huang","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"5987","DOI":"10.1073\/pnas.1220927110","article-title":"CCDC41 is required for ciliary vesicle docking to the mother centriole","volume":"110","author":"Joo","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"19691","DOI":"10.1073\/pnas.1210916109","article-title":"ARL13B, PDE6D, and CEP164 form a functional network for INPP5E ciliary targeting","volume":"109","author":"Humbert","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.cell.2012.06.028","article-title":"Exome capture reveals ZNF423 and CEP164 mutations, linking renal ciliopathies to DNA damage response signaling","volume":"150","author":"Chaki","year":"2012","journal-title":"Cell"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1016\/j.ekir.2021.02.005","article-title":"Genetic Background and Clinicopathologic Features of Adult-onset Nephronophthisis","volume":"6","author":"Fujimaru","year":"2021","journal-title":"Kidney Int. Rep."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"34764","DOI":"10.1038\/srep34764","article-title":"Genetic and clinical characterization of Pakistani families with Bardet-Biedl syndrome extends the genetic and phenotypic spectrum","volume":"6","author":"Maria","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1007\/s00439-020-02170-2","article-title":"An exome-first approach to aid in the diagnosis of primary ciliary dyskinesia","volume":"139","author":"Shamseldin","year":"2020","journal-title":"Hum. Genet."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Siller, S.S., Sharma, H., Li, S., Yang, J., Zhang, Y., Holtzman, M.J., Winuthayanon, W., Colognato, H., Holdener, B.C., and Li, F.Q. (2017). Conditional knockout mice for the distal appendage protein CEP164 reveal its essential roles in airway multiciliated cell differentiation. PLoS Genet., 13.","DOI":"10.1371\/journal.pgen.1007128"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1002\/humu.22477","article-title":"Ciliary Genes TBC 1 D 32\/C6orf170 and SCLT 1 are Mutated in Patients with OFD Type IX","volume":"35","author":"Adly","year":"2014","journal-title":"Hum. Mutat."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1007\/s13730-020-00472-y","article-title":"Bardet-Biedl syndrome in two unrelated patients with identical compound heterozygous SCLT1 mutations","volume":"9","author":"Morisada","year":"2020","journal-title":"CEN Case Rep."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1083\/jcb.200707181","article-title":"CEP164, a novel centriole appendage protein required for primary cilium formation","volume":"179","author":"Graser","year":"2007","journal-title":"J. Cell Biol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1083\/jcb.201202126","article-title":"Cep164 mediates vesicular docking to the mother centriole during early steps of ciliogenesis","volume":"199","author":"Schmidt","year":"2012","journal-title":"J. Cell Biol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1083\/jcb.201406140","article-title":"Chibby promotes ciliary vesicle formation and basal body docking during airway cell differentiation","volume":"207","author":"Burke","year":"2014","journal-title":"J. Cell Biol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/j.cell.2012.10.010","article-title":"The spinocerebellar ataxia-associated gene Tau tubulin kinase 2 controls the initiation of ciliogenesis","volume":"151","author":"Goetz","year":"2012","journal-title":"Cell"},{"key":"ref_113","first-page":"1","article-title":"Molecular mechanisms underlying the role of the centriolar CEP164-TTBK2 complex in ciliopathies","volume":"6","author":"Silva","year":"2021","journal-title":"Structure"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"e1700132","DOI":"10.1002\/bies.201700132","article-title":"Primary Cilia Reconsidered in the Context of Ciliopathies: Extraciliary and Ciliary Functions of Cilia Proteins Converge on a Polarity theme?","volume":"40","author":"Hua","year":"2018","journal-title":"BioEssays News Rev. Mol. Cell. Dev. Biol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1007\/s00018-017-2740-5","article-title":"Primary cilia proteins: Ciliary and extraciliary sites and functions","volume":"75","author":"Hua","year":"2018","journal-title":"Cell. Mol. Life Sci. CMLS"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1242\/bio.20134457","article-title":"Primary ciliogenesis requires the distal appendage component Cep123","volume":"2","author":"Sillibourne","year":"2013","journal-title":"Biol. Open"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.tcb.2011.03.006","article-title":"Rabs and the exocyst in ciliogenesis, tubulogenesis and beyond","volume":"21","author":"Das","year":"2011","journal-title":"Trends Cell Biol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1016\/j.cell.2007.03.053","article-title":"A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis","volume":"129","author":"Nachury","year":"2007","journal-title":"Cell"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.devcel.2008.07.004","article-title":"CP110 suppresses primary cilia formation through its interaction with CEP290, a protein deficient in human ciliary disease","volume":"15","author":"Tsang","year":"2008","journal-title":"Dev. Cell"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"3858","DOI":"10.1093\/hmg\/ddt241","article-title":"Bardet-Biedl syndrome proteins control the cilia length through regulation of actin polymerization","volume":"22","author":"Pravincumar","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/j.devcel.2009.12.022","article-title":"Ofd1, a human disease gene, regulates the length and distal structure of centrioles","volume":"18","author":"Singla","year":"2010","journal-title":"Dev. Cell"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1038\/ng1352","article-title":"The Bardet-Biedl protein BBS4 targets cargo to the pericentriolar region and is required for microtubule anchoring and cell cycle progression","volume":"36","author":"Kim","year":"2004","journal-title":"Nat. Genet."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1016\/j.celrep.2013.08.005","article-title":"LRRC45 is a centrosome linker component required for centrosome cohesion","volume":"4","author":"He","year":"2013","journal-title":"Cell Rep."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"2750","DOI":"10.1038\/ncomms3750","article-title":"Transition fibre protein FBF1 is required for the ciliary entry of assembled intraflagellar transport complexes","volume":"4","author":"Wei","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.ceb.2015.04.015","article-title":"The essential roles of transition fibers in the context of cilia","volume":"35","author":"Wei","year":"2015","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Kim, K., Lee, K., and Rhee, K. (2012). CEP90 is required for the assembly and centrosomal accumulation of centriolar satellites, which is essential for primary cilia formation. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0048196"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"e07519","DOI":"10.7554\/eLife.07519","article-title":"Centriolar satellites assemble centrosomal microcephaly proteins to recruit CDK2 and promote centriole duplication","volume":"4","author":"Kodani","year":"2015","journal-title":"eLife"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"3796","DOI":"10.1093\/hmg\/ddn277","article-title":"CEP290 interacts with the centriolar satellite component PCM-1 and is required for Rab8 localization to the primary cilium","volume":"17","author":"Kim","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1126\/science.283.5403.851","article-title":"Requirement of Cdk2-cyclin E activity for repeated centrosome reproduction in Xenopus egg extracts","volume":"283","author":"Hinchcliffe","year":"1999","journal-title":"Science"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1158\/0008-5472.CAN-10-2684","article-title":"Cep63 recruits Cdk1 to the centrosome: Implications for regulation of mitotic entry, centrosome amplification, and genome maintenance","volume":"71","author":"Fechter","year":"2011","journal-title":"Cancer Res."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"134","DOI":"10.3389\/fphys.2019.00134","article-title":"The Frog Xenopus as a Model to Study Joubert Syndrome: The Case of a Human Patient with Compound Heterozygous Variants in PIBF1","volume":"10","author":"Ott","year":"2019","journal-title":"Front. Physiol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1038\/ncb3201","article-title":"An siRNA-based functional genomics screen for the identification of regulators of ciliogenesis and ciliopathy genes","volume":"17","author":"Wheway","year":"2015","journal-title":"Nat. Cell Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/22\/12253\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:29:28Z","timestamp":1760167768000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/22\/12253"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,12]]},"references-count":132,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["ijms222212253"],"URL":"https:\/\/doi.org\/10.3390\/ijms222212253","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,12]]}}}