{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T14:19:35Z","timestamp":1791123575568,"version":"4.1.0"},"reference-count":101,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2019,2,2]],"date-time":"2019-02-02T00:00:00Z","timestamp":1549065600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010231","name":"Banting Research Foundation","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100010231","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The neuronal ceroid lipofuscinoses (NCLs) are a group of devastating neurological disorders that have a global distribution and affect people of all ages. Commonly known as Batten disease, this form of neurodegeneration is linked to mutations in 13 genetically distinct genes. The precise mechanisms underlying the disease are unknown, in large part due to our poor understanding of the functions of NCL proteins. The social amoeba Dictyostelium discoideum has proven to be an exceptional model organism for studying a wide range of neurological disorders, including the NCLs. The Dictyostelium genome contains homologs of 11 of the 13 NCL genes. Its life cycle, comprised of both single-cell and multicellular phases, provides an excellent system for studying the effects of NCL gene deficiency on conserved cellular and developmental processes. In this review, we highlight recent advances in NCL research using Dictyostelium as a biomedical model.<\/jats:p>","DOI":"10.3390\/cells8020115","type":"journal-article","created":{"date-parts":[[2019,2,5]],"date-time":"2019-02-05T11:31:07Z","timestamp":1549366267000},"page":"115","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Recent Insights into NCL Protein Function Using the Model Organism Dictyostelium discoideum"],"prefix":"10.3390","volume":"8","author":[{"given":"Meagan D.","family":"McLaren","sequence":"first","affiliation":[{"name":"Department of Biology, Trent University, 1600 West Bank Drive, Peterborough, ON K9L 0G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabateeshan","family":"Mathavarajah","sequence":"additional","affiliation":[{"name":"Department of Biology, Trent University, 1600 West Bank Drive, Peterborough, ON K9L 0G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Huber","sequence":"additional","affiliation":[{"name":"Department of Biology, Trent University, 1600 West Bank Drive, Peterborough, ON K9L 0G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2237","DOI":"10.1016\/j.bbadis.2015.05.011","article-title":"Genetics of the neuronal ceroid lipofuscinoses (Batten disease)","volume":"1852","author":"Mole","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2262","DOI":"10.1016\/j.bbadis.2015.05.007","article-title":"Human NCL neuropathology","volume":"1852","author":"Radke","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1016\/j.bbadis.2013.04.008","article-title":"NCL diseases\u2014Clinical perspectives","volume":"1832","author":"Schulz","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2242","DOI":"10.1016\/j.bbadis.2015.04.027","article-title":"Cell biology of the NCL proteins: What they do and don\u2019t do","volume":"1852","author":"Pearce","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1016\/j.bbadis.2013.01.009","article-title":"Use of model organisms for the study of neuronal ceroid lipofuscinosis","volume":"1832","author":"Bond","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.ejcb.2012.10.003","article-title":"Simple system\u2014Substantial share: The use of Dictyostelium in cell biology and molecular medicine","volume":"92","author":"Kortholt","year":"2013","journal-title":"Eur. J. Cell Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1186\/s12929-016-0301-0","article-title":"Using the social amoeba Dictyostelium to study the functions of proteins linked to neuronal ceroid lipofuscinosis","volume":"23","author":"Huber","year":"2016","journal-title":"J. Biomed. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/nature03481","article-title":"The genome of social amoeba Dictyostelium discoideum","volume":"435","author":"Eichinger","year":"2005","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"14.1.1","DOI":"10.1002\/cpet.15","article-title":"Dictyostelium discoideum: A model system for cell and developmental biology","volume":"15","author":"Mathavarajah","year":"2017","journal-title":"Curr. Protoc. Essent. Lab. Tech."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/978-1-62703-302-2_13","article-title":"The application of the Cre-loxP system for generating multiple knock-out and knock-in targeted loci","volume":"983","author":"Faix","year":"2013","journal-title":"Methods Mol. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"8471","DOI":"10.1038\/s41598-018-26756-z","article-title":"CRISPR\/Cas9 mediated targeting of multiple genes in Dictyostelium","volume":"8","author":"Sekine","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2267","DOI":"10.1242\/jcs.084285","article-title":"Identifying an uptake mechanism for the antiepileptic and bipolar disorder treatment valproic acid using the simple biomedical model Dictyostelium","volume":"124","author":"Terbach","year":"2011","journal-title":"J. Cell Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.nbd.2013.10.017","article-title":"Seizure-induced reduction in PIP3 levels contributes to seizure-activity and is rescued by valproic acid","volume":"62","author":"Chang","year":"2014","journal-title":"Neurobiol. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.semcdb.2010.10.005","article-title":"Lead genetic studies in Dictyostelium discoideum and translational studies in human cells demonstrate that sphingolipids are key regulators of sensitivity to cisplatin and other anticancer drugs","volume":"22","author":"Alexander","year":"2011","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.semcdb.2010.10.007","article-title":"Functional analyses of lissencephaly-related proteins in Dictyostelium","volume":"22","author":"Meyer","year":"2011","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.semcdb.2010.11.001","article-title":"Dictyostelium as a model for human lysosomal and trafficking diseases","volume":"22","author":"Maniak","year":"2011","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/1423-0127-19-41","article-title":"Clues to \u03b3-secretase, huntingtin and Hirano body normal function using the model organism Dictyostelium discoideum","volume":"19","author":"Myre","year":"2012","journal-title":"J. Biomed. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1042\/BST20130183","article-title":"The search for better epilepsy treatments: From slime mould to coconuts","volume":"41","author":"Walker","year":"2013","journal-title":"Biochem. Soc. Trans."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1016\/j.bbagen.2013.10.019","article-title":"Dictyostelium, a microbial model for brain disease","volume":"1840","author":"Annesley","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1080\/19336896.2015.1099799","article-title":"Protein misfolding in Dictyostelium: Using a freak of nature to gain insight into a universal problem","volume":"9","author":"Malinovska","year":"2015","journal-title":"Prion"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1002\/humu.22292","article-title":"Autosomal recessive spinocerebellar ataxia 7 (SCAR7) is caused by variants in TPP1, the gene involved in classic late-infantile neuronal ceroid lipofuscinosis 2 disease (CLN2 disease)","volume":"34","author":"Sun","year":"2013","journal-title":"Hum. Mutat."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1802","DOI":"10.1126\/science.277.5333.1802","article-title":"Association of mutations in a lysosomal protein with classical late-infantile neuronal ceroid lipofuscinosis","volume":"277","author":"Sleat","year":"1997","journal-title":"Science"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Vidal-Donet, J.M., C\u00e1rcel-Trullols, J., Casanova, B., Aguado, C., and Knecht, E. (2013). Alterations in ROS activity and lysosomal pH account for distinct patterns of macroautophagy in LINCL and JNCL fibroblasts. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0055526"},{"key":"ref_24","first-page":"147","article-title":"Partial genetic suppression of a loss-of-function mutant of the neuronal ceroid lipofuscinosis-associated protease TPP1 in Dictyostelium discoideum","volume":"8","author":"Phillips","year":"2015","journal-title":"Dis. Models Mech."},{"key":"ref_25","first-page":"897","article-title":"A tripeptidyl peptidase 1 is a binding partner of the Golgi pH regulator (GPHR) in Dictyostelium","volume":"10","author":"Stumpf","year":"2017","journal-title":"Dis. Models Mech."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.plipres.2013.06.004","article-title":"Oxysterol-binding proteins: Sterol and phosphoinositide sensors coordinating transport, signaling and metabolism","volume":"52","author":"Olkkonen","year":"2013","journal-title":"Prog. Lipid Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s13023-018-0798-2","article-title":"Neural stem cells for disease modeling and evaluation of therapeutics for infantile (CLN1\/PPT1) and late infantile (CLN2\/TPP1) neuronal ceroid lipofuscinoses","volume":"13","author":"Sima","year":"2018","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.nbd.2018.04.010","article-title":"Modulating membrane fluidity corrects Batten disease phenotypes in vitro and in vivo","volume":"115","author":"Schultz","year":"2018","journal-title":"Neurobiol. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1038\/ncb1773","article-title":"GPHR is a novel anion channel critical for acidification and functions of the Golgi apparatus","volume":"10","author":"Maeda","year":"2008","journal-title":"Nat. Cell Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1242\/bio.20137187","article-title":"Mutations in the Drosophila ortholog of the vertebrate Golgi pH regulator (GPHR) protein disturb endoplasmic reticulum and Golgi organization and affect systemic growth","volume":"3","author":"Charroux","year":"2014","journal-title":"Biol. Open"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1128\/EC.00208-14","article-title":"The Dictyostelium discoideum GPHR ortholog is an endoplasmic reticulum and Golgi protein with roles during development","volume":"14","author":"Deckstein","year":"2015","journal-title":"Eukaryot. Cell"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.cellsig.2017.03.022","article-title":"Loss of Cln3 impacts protein secretion in the social amoeba Dictyostelium","volume":"35","author":"Huber","year":"2017","journal-title":"Cell. Signal."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Rot, G., Parikh, A., Curk, T., Kuspa, A., Shaulsky, G., and Zupan, B. (2009). dictyExpress: A Dictyostelium discoideum gene expression database with an explorative data analysis web-based interface. BMC Bioinform., 10.","DOI":"10.1186\/1471-2105-10-265"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"79","DOI":"10.2217\/clp.11.70","article-title":"The juvenile Batten disease protein, CLN3, and its role in regulating anterograde and retrograde post-Golgi trafficking","volume":"7","author":"Cotman","year":"2012","journal-title":"Clin. Lipidol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Ratajczak, E., Petcherski, A., Ramos-Moreno, J., and Ruonala, M.O. (2014). FRET-assisted determination of CLN3 membrane topology. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0102593"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2860","DOI":"10.1242\/jcs.030122","article-title":"Btn1 affects cytokinesis and cell-wall deposition by independent mechanisms, one of which is linked to dysregulation of vacuole pH","volume":"121","author":"Codlin","year":"2008","journal-title":"J. Cell Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"C1388","DOI":"10.1152\/ajpcell.00272.2009","article-title":"Osmoregulation of ceroid neuronal lipofuscinosis type 3 in the renal medulla","volume":"298","author":"Stein","year":"2010","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Getty, A., Kov\u00e1cs, A.D., Lengyel-Nelson, T., Cardillo, A., Hof, C., Chan, C.H., and Pearce, D.A. (2013). Osmotic stress changes the expression and subcellular localization of the Batten disease protein CLN3. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0066203"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"18065","DOI":"10.1523\/JNEUROSCI.0498-13.2013","article-title":"CLN3 loss disturbs membrane microdomain properties and protein transport in brain endothelial cells","volume":"33","author":"Tecedor","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Huber, R.J., Myre, M.A., and Cotman, S.L. (2014). Loss of Cln3 function in the social amoeba Dictyostelium discoideum causes pleiotropic effects that are rescued by human CLN3. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0110544"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.yexmp.2014.10.003","article-title":"Neuronal ceroid lipofuscinosis genes, CLN2, CLN3 and CLN5 are spatially and temporally co-expressed in a developing mouse brain","volume":"97","author":"Fabritius","year":"2014","journal-title":"Exp. Mol. Pathol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"6635","DOI":"10.3892\/mmr.2015.4238","article-title":"RNAi-mediated knockdown of the CLN3 gene inhibits proliferation and promotes apoptosis in drug-resistant ovarian cancer cells","volume":"12","author":"Mao","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"14361","DOI":"10.1074\/jbc.M114.621706","article-title":"Unbiased cell-based screening in a neuronal cell model of Batten disease highlights an interaction between Ca2+ homeostasis, autophagy, and CLN3 protein function","volume":"290","author":"Chandrachud","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1007\/s11626-015-9979-7","article-title":"Fibrates inhibit the apoptosis of Batten disease lymphoblast cells via autophagy recovery and regulation of mitochondrial membrane potential","volume":"52","author":"Hong","year":"2016","journal-title":"In Vitro Cell. Dev. Biol. Anim."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1080\/19336918.2016.1236179","article-title":"Aberrant adhesion impacts early development in a Dictyostelium model for juvenile neuronal ceroid lipofuscinosis","volume":"11","author":"Huber","year":"2017","journal-title":"Cell Adhes. Migr."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/s40478-017-0476-y","article-title":"Glial cells are functionally impaired in juvenile neuronal ceroid lipofuscinosis and detrimental to neurons","volume":"5","author":"Parviainen","year":"2017","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3787","DOI":"10.1021\/acs.jproteome.7b00460","article-title":"Proteomic analysis of brain and cerebrospinal fluid from the three major forms of neuronal ceroid lipofuscinosis reveals potential biomarkers","volume":"16","author":"Sleat","year":"2017","journal-title":"J. Proteome Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3559","DOI":"10.1016\/j.bbadis.2018.08.013","article-title":"Cln3 function is linked to osmoregulation in a Dictyostelium model of Batten disease","volume":"1864","author":"Mathavarajah","year":"2018","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2064","DOI":"10.1038\/emboj.2008.131","article-title":"Regulation of contractile vacuole formation and activity in Dictyostelium","volume":"27","author":"Du","year":"2008","journal-title":"EMBO J."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1111\/febs.12203","article-title":"Ca2+-calmodulin interacts with DdCAD-1 and promotes DdCAD-1 transport by contractile vacuoles in Dictyostelium cells","volume":"280","author":"Sriskanthadevan","year":"2013","journal-title":"FEBS J."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/B978-0-12-407694-5.00009-2","article-title":"Contractile vacuole complex\u2014Its expanding protein inventory","volume":"306","author":"Plattner","year":"2013","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Bosch, M.E., and Kielian, T. (2018). Astrocytes in juvenile neuronal ceroid lipofuscinosis (CLN3) display metabolic and calcium signaling abnormalities. J. Neurochem.","DOI":"10.1111\/jnc.14545"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/j.1469-7793.2001.0003g.x","article-title":"Receptor-mediated control of regulatory volume decrease (RVD) and apoptotic volume decrease (AVD)","volume":"532","author":"Okada","year":"2001","journal-title":"J. Physiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"7832","DOI":"10.1016\/S0021-9258(17)34446-0","article-title":"Inhibition of the degradation of receptor-bound human choriogonadotropin by lysosomotropic agents, protease inhibitors, and metabolic inhibitors","volume":"253","author":"Ascoli","year":"1978","journal-title":"J. Biol. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3710","DOI":"10.1093\/bioinformatics\/bth456","article-title":"GO: TermFinder\u2014Open source software for accessing Gene Ontology information and finding significantly enriched Gene Ontology terms associated with a list of genes","volume":"20","author":"Boyle","year":"2004","journal-title":"Bioinformatics"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"D447","DOI":"10.1093\/nar\/gku1003","article-title":"STRING v10: Protein-protein interaction networks, integrated over the tree of life","volume":"43","author":"Szklarczyk","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1002\/cm.970180105","article-title":"Cell division in Dictyostelium with special emphasis on actomyosin organization in cytokinesis","volume":"18","author":"Fukui","year":"1991","journal-title":"Cell Motil. Cytoskeleton"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1242\/jcs.104.4.1119","article-title":"Calmodulin and the contractile vacuole complex in mitotic cells of Dictyostelium discoideum","volume":"104","author":"Zhu","year":"1993","journal-title":"J. Cell Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1242\/jcs.110.2.123","article-title":"Myosin II-independent processes in mitotic cells of Dictyostelium discoideum: Redistribution of the nuclei, re-arrangement of the actin system and formation of the cleavage furrow","volume":"110","author":"Neujahr","year":"1997","journal-title":"J. Cell Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1091\/mbc.10.1.225","article-title":"Disruption of a dynamin homologue affects endocytosis, organelle morphology, and cytokinesis in Dictyostelium discoideum","volume":"10","author":"Wienke","year":"1999","journal-title":"Mol. Biol. Cell"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"4539","DOI":"10.1093\/emboj\/cdf449","article-title":"Defects in cytokinesis, actin reorganization and the contractile vacuole in cells deficient in RhoGDI","volume":"21","author":"Rivero","year":"2002","journal-title":"EMBO J."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1034\/j.1600-0854.2002.30107.x","article-title":"The Dictyostelium LvsA protein is localized on the contractile vacuole and is required for osmoregulation","volume":"3","author":"Gerald","year":"2002","journal-title":"Traffic"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4553","DOI":"10.1242\/dev.02032","article-title":"A secreted factor represses cell proliferation in Dictyostelium","volume":"132","author":"Brock","year":"2005","journal-title":"Development"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2473","DOI":"10.1242\/jcs.026682","article-title":"The secreted Dictyostelium protein CfaD is a chalone","volume":"121","author":"Bakthavatsalam","year":"2008","journal-title":"J. Cell Sci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"10990","DOI":"10.1073\/pnas.1206350109","article-title":"A secreted protein is an endogenous chemorepellant in Dictyostelium discoideum","volume":"109","author":"Phillips","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1242\/dev.112.1.269","article-title":"A secreted 80 \u00d7 103 Mr protein mediates sensing of cell density and the onset of development in Dictyostelium","volume":"112","author":"Gomer","year":"1991","journal-title":"Development"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3883","DOI":"10.1002\/jcb.26039","article-title":"Role of the lysosomal membrane protein, CLN3, in the regulation of cathepsin D activity","volume":"118","author":"Kovacs","year":"2017","journal-title":"J. Cell. Biochem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1055\/s-2007-981449","article-title":"Revelation of a novel CLN5 mutation in early juvenile neuronal ceroid lipofuscinosis","volume":"38","author":"Cannelli","year":"2007","journal-title":"Neuropediatrics"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/s00415-014-7553-y","article-title":"Adult-onset autosomal recessive ataxia associated with neuronal ceroid lipofuscinosis type 5 gene (CLN5) mutations","volume":"262","author":"Mancini","year":"2015","journal-title":"J. Neurol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1038\/975","article-title":"CLN5, a novel gene encoding a putative transmembrane protein mutated in Finnish variant late infantile neuronal ceroid lipofuscinosis","volume":"19","author":"Savukoski","year":"1998","journal-title":"Nat. Genet."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1212\/WNL.0b013e3181cff70d","article-title":"CLN5 mutations are frequent in juvenile and late-onset non-Finnish patients with NCL","volume":"74","author":"Xin","year":"2010","journal-title":"Neurology"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/1750-1172-8-19","article-title":"Molecular epidemiology of childhood neuronal ceroid-lipofuscinosis in Italy","volume":"8","author":"Santorelli","year":"2013","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1111\/dmcn.13473","article-title":"Phenotype and natural history of variant late infantile ceroid-lipofuscinosis 5","volume":"59","author":"Simonati","year":"2017","journal-title":"Dev. Med. Child Neurol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1093\/hmg\/11.8.885","article-title":"Lysosomal localization of the neuronal ceroid lipofuscinosis CLN5 protein","volume":"11","author":"Isosomppi","year":"2002","journal-title":"Hum. Mol. Genet."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Moharir, A., Peck, S.H., Budden, T., and Lee, S.Y. (2013). The role of N-glycosylation in folding, trafficking, and functionality of lysosomal protein CLN5. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0074299"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.nbd.2013.11.011","article-title":"Inhibition of storage pathology in prenatal CLN5-deficient sheep neural cultures by lentiviral gene therapy","volume":"62","author":"Hughes","year":"2014","journal-title":"Neurobiol. Dis."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.cellsig.2017.11.001","article-title":"Cln5 is secreted and functions as a glycoside hydrolase in Dictyostelium","volume":"42","author":"Huber","year":"2018","journal-title":"Cell. Signal."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1002\/humu.22443","article-title":"Topology and membrane anchoring of the lysosomal storage disease-related protein CLN5","volume":"34","author":"Larkin","year":"2013","journal-title":"Hum. Mutat."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.yexcr.2015.08.021","article-title":"Proteolytic processing of the neuronal ceroid lipofuscinosis related lysosomal protein CLN5","volume":"338","author":"Adams","year":"2015","journal-title":"Exp. Cell Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.yexcr.2017.04.024","article-title":"CLN5 is cleaved by members of the SPP\/SPPL family to produce a mature soluble protein","volume":"357","author":"Jules","year":"2017","journal-title":"Exp. Cell Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1128\/MCB.06726-11","article-title":"The role of ceroid lipofuscinosis neuronal protein 5 (CLN5) in endosomal sorting","volume":"32","author":"Mamo","year":"2012","journal-title":"Mol. Cell. Biol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.nbd.2011.12.009","article-title":"Cln5-deficiency in mice leads to microglial activation, defective myelination and changes in lipid metabolism","volume":"46","author":"Schmiedt","year":"2012","journal-title":"Neurobiol. Dis."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"3798","DOI":"10.1002\/elps.201200472","article-title":"CLN5 and CLN8 protein association with ceramide synthase: Biochemical and proteomic approaches","volume":"33","author":"Haddad","year":"2012","journal-title":"Electrophoresis"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1038\/s41598-017-01716-1","article-title":"Retinal degeneration in a mouse model of CLN5 disease is associated with compromised autophagy","volume":"7","author":"Leinonen","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/s41598-018-36379-z","article-title":"Autophagy-lysosome pathway alterations and alpha-synuclein up-regulation in the subtype of neuronal ceroid lipofuscinosis, CLN5 disease","volume":"9","author":"Adams","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1016\/j.bbamcr.2018.07.017","article-title":"Secretion and function of Cln5 during the early stages of Dictyostelium development","volume":"1865","author":"Huber","year":"2018","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1080\/15548627.2016.1226737","article-title":"Autophagy in Dictyostelium: Mechanisms, regulation and disease in a simple biomedical model","volume":"13","author":"Mesquita","year":"2017","journal-title":"Autophagy"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1002\/jcp.1041160116","article-title":"Degradation of microinjected proteins: Effects of lysosomotropic agents and inhibitors of autophagy","volume":"116","author":"Rote","year":"1983","journal-title":"J. Cell. Physiol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1139\/m79-221","article-title":"Aggregation during sexual development in Dictyostelium discoideum","volume":"25","year":"1979","journal-title":"Can. J. Microbiol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1002\/ana.20187","article-title":"Impaired cell adhesion and apoptosis in a novel CLN9 Batten disease variant","volume":"56","author":"Schulz","year":"2004","journal-title":"Ann. Neurol."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"von Schantz, C., Saharinen, J., Kopra, O., Cooper, J.D., Gentile, M., Hovatta, I., Peltonen, L., and Jalanko, A. (2008). Brain gene expression profiles of Cln1 and Cln5 deficient mice unravels common molecular pathways underlying neuronal degeneration in NCL diseases. BMC Genom., 9.","DOI":"10.1186\/1471-2164-9-146"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1203\/pdr.0b013e31802d8a4a","article-title":"Neuronal ceroid lipofuscinosis: A common pathway?","volume":"61","author":"Mousallem","year":"2007","journal-title":"Pediatr. Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2410","DOI":"10.1091\/mbc.e02-01-0031","article-title":"Neuronal ceroid lipofuscinoses are connected at molecular level: Interaction of CLN5 protein with CLN2 and CLN3","volume":"13","author":"Vesa","year":"2002","journal-title":"Mol. Biol. Cell"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Lyly, A., von Schantz, C., Heine, C., Schmiedt, M.L., Sipil\u00e4, T., Jalanko, A., and Kytt\u00e4l\u00e4, A. (2009). Novel interactions of CLN5 support molecular networking between neuronal ceroid lipofuscinosis proteins. BMC Cell Biol., 10.","DOI":"10.1186\/1471-2121-10-83"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.1021\/pr301125k","article-title":"Drafting the CLN3 protein interactome in SH-SY5Y human neuroblastoma cells: A label-free quantitative proteomics approach","volume":"12","author":"Scifo","year":"2013","journal-title":"J. Proteome Res."},{"key":"ref_96","first-page":"342","article-title":"Exacerbated neuronal ceroid lipofuscinosis phenotype in Cln1\/5 double-knockout mice","volume":"6","author":"Blom","year":"2013","journal-title":"Dis. Models Mech."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1093\/hmg\/ddy076","article-title":"Loss of CLN7 results in depletion of soluble lysosomal proteins and impaired mTOR reactivation","volume":"27","author":"Danyukova","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1002\/pmic.201100313","article-title":"Investigating the macropinocytic proteome of Dictyostelium amoebae by high-resolution mass spectrometry","volume":"12","author":"Journet","year":"2012","journal-title":"Proteomics"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.1007\/s12035-014-8832-4","article-title":"Genetic convergence of Parkinson\u2019s disease and lysosomal storage disorders","volume":"51","author":"Deng","year":"2015","journal-title":"Mol. Neurobiol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"12752","DOI":"10.1038\/srep12752","article-title":"Comprehensive functional characterization of murine infantile Batten disease including Parkinson-like behavior and dopaminergic markers","volume":"5","author":"Dearborn","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"e00011-18","DOI":"10.1128\/MCB.00011-18","article-title":"An Alzheimer\u2019s disease-linked loss-of-function CLN5 variant impairs cathepsin D maturation, consistent with a retromer trafficking defect","volume":"38","author":"Qureshi","year":"2018","journal-title":"Mol. Cell. Biol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/8\/2\/115\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:30:45Z","timestamp":1760185845000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/8\/2\/115"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,2]]},"references-count":101,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2019,2]]}},"alternative-id":["cells8020115"],"URL":"https:\/\/doi.org\/10.3390\/cells8020115","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,2]]}}}