{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T22:46:05Z","timestamp":1791413165176,"version":"4.3.3"},"reference-count":59,"publisher":"The Company of Biologists","issue":"21","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,11,1]]},"abstract":"<jats:p>The retromer complex is required for the efficient endosome-to-Golgi retrieval of the CIMPR, sortilin, SORL1, wntless and other physiologically important membrane proteins. Retromer comprises two protein complexes that act together in endosome-to-Golgi retrieval; the cargo-selective complex is a trimer of VPS35, VPS29 and VPS26 that sorts cargo into tubules for retrieval to the Golgi. Tubules are produced by the oligomerization of sorting nexin dimers. Here, we report the identification of five endosomally-localised proteins that modulate tubule formation and are recruited to the membrane via interactions with the cargo-selective retromer complex. One of the retromer-interacting proteins, strumpellin, is mutated in hereditary spastic paraplegia, a progressive length-dependent axonopathy. Here, we show that strumpellin regulates endosomal tubules as part of a protein complex with three other proteins that include WASH1, an actin-nucleating promoting factor. Therefore, in addition to a direct role in endosome-to-Golgi retrieval, the cargo-selective retromer complex also acts as a platform for recruiting physiologically important proteins to endosomal membranes that regulate membrane tubule dynamics.<\/jats:p>","DOI":"10.1242\/jcs.071472","type":"journal-article","created":{"date-parts":[[2010,10,6]],"date-time":"2010-10-06T00:25:43Z","timestamp":1286324743000},"page":"3703-3717","source":"Crossref","is-referenced-by-count":246,"title":["The cargo-selective retromer complex is a recruiting hub for protein complexes that regulate endosomal tubule dynamics"],"prefix":"10.1242","volume":"123","author":[{"given":"Michael E.","family":"Harbour","sequence":"first","affiliation":[{"name":"Department of Clinical Biochemistry, University of Cambridge, Cambridge Institute for Medical Research, Wellcome Trust\/MRC Building, Addenbrookes Hospital, Cambridge CB2 0XY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia Y. A.","family":"Breusegem","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, University of Cambridge, Cambridge Institute for Medical Research, Wellcome Trust\/MRC Building, Addenbrookes Hospital, Cambridge CB2 0XY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Antrobus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Freeman","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, University of Cambridge, Cambridge Institute for Medical Research, Wellcome Trust\/MRC Building, Addenbrookes Hospital, Cambridge CB2 0XY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan","family":"Reid","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, University of Cambridge, Cambridge Institute for Medical Research, Wellcome Trust\/MRC Building, Addenbrookes Hospital, Cambridge CB2 0XY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew N. J.","family":"Seaman","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, University of Cambridge, Cambridge Institute for Medical Research, Wellcome Trust\/MRC Building, Addenbrookes Hospital, Cambridge CB2 0XY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042521173111800_R1","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1083\/jcb.200312055","article-title":"Role of the mammalian retromer in sorting of the cation-independent mannose 6-phosphate receptor","volume":"165","author":"Arighi","year":"2004","journal-title":"J. Cell Biol."},{"key":"2021042521173111800_R2","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.advenzreg.2009.10.002","article-title":"The retromer complex","volume":"50","author":"Attar","year":"2009","journal-title":"Adv Enzyme Regul."},{"key":"2021042521173111800_R3","doi-asserted-by":"crossref","first-page":"12513","DOI":"10.1074\/jbc.M210843200","article-title":"STAM and Hrs are subunits of a multivalent ubiquitin-binding complex on early endosomes","volume":"278","author":"Bache","year":"2003","journal-title":"J. Biol. Chem."},{"key":"2021042521173111800_R4","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.ceb.2008.03.009","article-title":"Retromer","volume":"20","author":"Bonifacino","year":"2008","journal-title":"Curr. Opin. Cell Biol."},{"key":"2021042521173111800_R5","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1016\/j.cub.2004.09.077","article-title":"Sorting nexin-1 mediates tubular endosome-to-TGN transport through coincidence sensing of high-curvature membranes and 3-phosphoinositides","volume":"14","author":"Carlton","year":"2004","journal-title":"Curr. Biol."},{"key":"2021042521173111800_R6","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1111\/j.1600-0854.2008.00777.x","article-title":"The structure and function of the retromer protein complex","volume":"9","author":"Collins","year":"2008","journal-title":"Traffic"},{"key":"2021042521173111800_R7","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1038\/nsmb954","article-title":"Vps29 has a phosphoesterase fold that acts as a protein interaction scaffold for retromer assembly","volume":"12","author":"Collins","year":"2005","journal-title":"Nat. Struct. Mol. Biol."},{"key":"2021042521173111800_R8","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1038\/nbt.1511","article-title":"MaxQuant enables high peptide identification rates, individualised p.p.b.-range mass accuracies and proteome-wide protein quantification","volume":"26","author":"Cox","year":"2008","journal-title":"Nat. Biotechnol."},{"key":"2021042521173111800_R9","doi-asserted-by":"crossref","first-page":"2977","DOI":"10.1242\/jcs.013250","article-title":"Evolution of the eukaryotic membrane-trafficking system: origin, tempo and mode","volume":"120","author":"Dacks","year":"2007","journal-title":"J. Cell Sci."},{"key":"2021042521173111800_R10","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1016\/j.devcel.2009.09.010","article-title":"The Arp2\/3 activator WASH controls the fission of endosomes through a large multiprotein complex","volume":"17","author":"Derivery","year":"2009","journal-title":"Dev Cell."},{"key":"2021042521173111800_R11","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.cell.2009.07.052","article-title":"GOLPH3 bridges phosphatidylinositol-4-phosphate and actomyosin to stretch and shape the Golgi to promote budding","volume":"139","author":"Dippold","year":"2009","journal-title":"Cell"},{"key":"2021042521173111800_R12","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.devcel.2007.12.014","article-title":"Retromer retrieves wntless","volume":"14","author":"Eaton","year":"2008","journal-title":"Dev. Cell"},{"key":"2021042521173111800_R13","doi-asserted-by":"crossref","first-page":"2801","DOI":"10.1007\/s00018-008-8351-4","article-title":"Regulation of secretory vesicle traffic by Rab small GTPases","volume":"65","author":"Fukuda","year":"2008","journal-title":"Cell. Mol. Life Sci."},{"key":"2021042521173111800_R14","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.1111\/j.1600-0854.2007.00652.x","article-title":"EHD1 interacts with retromer to stabilize SNX1 tubules and facilitate endosome-to-Golgi retrieval","volume":"8","author":"Gokool","year":"2007","journal-title":"Traffic"},{"key":"2021042521173111800_R15","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1042\/BJ20070555","article-title":"Identification of a conserved motif required for Vps35p\/Vps26p interaction and assembly of the retromer complex","volume":"408","author":"Gokool","year":"2007","journal-title":"Biochem. J."},{"key":"2021042521173111800_R16","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1016\/j.devcel.2009.09.009","article-title":"A FAM21-containing WASH complex regulates retromer-dependent sorting","volume":"17","author":"Gomez","year":"2009","journal-title":"Dev. Cell"},{"key":"2021042521173111800_R17","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1038\/nature01167","article-title":"TRF2 associates with DREF and directs promoter-selective gene expression in Drosophila","volume":"420","author":"Hochheimer","year":"2002","journal-title":"Nature"},{"key":"2021042521173111800_R18","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1038\/cr.2009.130","article-title":"The retromer component SNX6 interacts with dynactin p150(Glued) and mediates endosome-to-TGN transport","volume":"19","author":"Hong","year":"2009","journal-title":"Cell Res."},{"key":"2021042521173111800_R19","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.cell.2009.05.025","article-title":"A class of dynamin-like GTPases involved in the generation of the tubular ER network","volume":"138","author":"Hu","year":"2009","journal-title":"Cell"},{"key":"2021042521173111800_R20","doi-asserted-by":"crossref","first-page":"6045","DOI":"10.1073\/pnas.0800159105","article-title":"TRIM21 is an IgG receptor that is structurally, thermodynamically, and kinetically conserved","volume":"105","author":"Keeble","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2021042521173111800_R21","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.1002\/pmic.200300721","article-title":"The International Protein Index: an integrated database for proteomics experiments","volume":"4","author":"Kersey","year":"2004","journal-title":"Proteomics"},{"key":"2021042521173111800_R22","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1007\/s11910-008-0060-8","article-title":"The neuronal sortilin-related receptor gene SORL1 and late-onset Alzheimer's disease","volume":"8","author":"Lee","year":"2008","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"2021042521173111800_R23","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/j.cell.2006.03.032","article-title":"A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration","volume":"125","author":"Lim","year":"2006","journal-title":"Cell"},{"key":"2021042521173111800_R24","doi-asserted-by":"crossref","first-page":"e237","DOI":"10.1371\/journal.pgen.0030237","article-title":"Human subtelomeric WASH genes encode a new subclass of the WASP family","volume":"3","author":"Linardopoulou","year":"2007","journal-title":"PLoS Genet."},{"key":"2021042521173111800_R25","doi-asserted-by":"crossref","first-page":"2849","DOI":"10.1242\/dev.035246","article-title":"Wash functions downstream of Rho and links linear and branched actin nucleation factors","volume":"136","author":"Liu","year":"2009","journal-title":"Development"},{"key":"2021042521173111800_R26","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1111\/j.1471-4159.2009.06258.x","article-title":"Atlastin-1, the dynamin-like GTPase responsible for spastic paraplegia SPG3A, remodels lipid membranes and may form tubules and vesicles in the endoplasmic reticulum","volume":"110","author":"Muriel","year":"2009","journal-title":"J. Neurochem."},{"key":"2021042521173111800_R27","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.bbrc.2006.05.113","article-title":"FKBP133: a novel mouse FK506-binding protein homolog alters growth cone morphology","volume":"346","author":"Nakajima","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2021042521173111800_R28","doi-asserted-by":"crossref","first-page":"6842","DOI":"10.1128\/MCB.00815-07","article-title":"Sorting by the cytoplasmic domain of the amyloid precursor protein binding receptor SorLA","volume":"27","author":"Nielsen","year":"2007","journal-title":"Mol. Cell. Biol."},{"key":"2021042521173111800_R29","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1111\/j.1600-0854.2010.01035.x","article-title":"Regulation of P2Y receptor traffic by sorting nexin 1 is retromer independent","volume":"11","author":"Nisar","year":"2010","journal-title":"Traffic"},{"key":"2021042521173111800_R30","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1038\/nature08280","article-title":"Homotypic fusion of ER membranes requires the dynamin-like GTPase atlastin","volume":"460","author":"Orso","year":"2009","journal-title":"Nature"},{"key":"2021042521173111800_R31","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1038\/nature04847","article-title":"TBC-domain GAPs for Rab GTPases accelerate GTP hydrolysis by a dual-finger mechanism","volume":"442","author":"Pan","year":"2006","journal-title":"Nature"},{"key":"2021042521173111800_R32","doi-asserted-by":"crossref","first-page":"3242","DOI":"10.1091\/mbc.12.10.3242","article-title":"Vps26p, a component of retromer, directs the interactions of Vps35p in endosome-to-Golgi retrieval","volume":"12","author":"Reddy","year":"2001","journal-title":"Mol. Biol. Cell"},{"key":"2021042521173111800_R33","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/ng1943","article-title":"The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease","volume":"39","author":"Rogaeva","year":"2007","journal-title":"Nat. Genet."},{"key":"2021042521173111800_R34","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1128\/MCB.00156-06","article-title":"Interchangeable but essential functions of SNX1 and SNX2 in the association of retromer with endosomes and the trafficking of mannose 6-phosphate receptors","volume":"27","author":"Rojas","year":"2007","journal-title":"Mol. Cell. Biol."},{"key":"2021042521173111800_R35","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1083\/jcb.200804048","article-title":"Regulation of retromer recruitment to endosomes by sequential action of Rab5 and Rab7","volume":"183","author":"Rojas","year":"2008","journal-title":"J. Cell Biol."},{"key":"2021042521173111800_R36","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1016\/j.yexcr.2008.09.021","article-title":"Signaling from endosomes: location makes a difference","volume":"315","author":"Sadowski","year":"2009","journal-title":"Exp. Cell Res."},{"key":"2021042521173111800_R37","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1042\/BST0370167","article-title":"ESCRTs and human disease","volume":"37","author":"Saksena","year":"2009","journal-title":"Biochem. Soc. Trans."},{"key":"2021042521173111800_R38","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1016\/S1474-4422(08)70258-8","article-title":"Hereditary spastic paraplegia: clinical features and pathogenetic mechanisms","volume":"7","author":"Salinas","year":"2008","journal-title":"Lancet. Neurol."},{"key":"2021042521173111800_R39","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1093\/hmg\/ddi447","article-title":"Spastin and atlastin, two proteins mutated in autosomal-dominant hereditary spastic paraplegia, are binding partners","volume":"15","author":"Sanderson","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"2021042521173111800_R40","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.tcb.2009.05.001","article-title":"Roles of endosomal trafficking in neurite outgrowth and guidance","volume":"19","author":"Sann","year":"2009","journal-title":"Trends Cell Biol."},{"key":"2021042521173111800_R41","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.devcel.2008.02.016","article-title":"Golgi localization of glycosyltransferases requires a Vps74p oligomer","volume":"14","author":"Schmitz","year":"2008","journal-title":"Dev. Cell."},{"key":"2021042521173111800_R42","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1212\/WNL.0b013e3181a6086c","article-title":"Autosomal dominant spastic paraplegia with peripheral neuropathy maps to chr12q23-24","volume":"72","author":"Sch\u00fcle","year":"2009","journal-title":"Neurology"},{"key":"2021042521173111800_R43","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1083\/jcb.200312034","article-title":"Cargo-selective endosomal sorting for retrieval to the Golgi requires retromer","volume":"165","author":"Seaman","year":"2004","journal-title":"J. Cell Biol."},{"key":"2021042521173111800_R44","doi-asserted-by":"crossref","first-page":"2378","DOI":"10.1242\/jcs.009654","article-title":"Identification of a novel conserved sorting motif required for retromer-mediated endosome-to-TGN retrieval","volume":"120","author":"Seaman","year":"2007","journal-title":"J. Cell Sci."},{"key":"2021042521173111800_R45","doi-asserted-by":"crossref","first-page":"2842","DOI":"10.1007\/s00018-008-8354-1","article-title":"Endosome protein sorting: motifs and machinery","volume":"65","author":"Seaman","year":"2008","journal-title":"Cell. Mol. Life Sci."},{"key":"2021042521173111800_R46","doi-asserted-by":"crossref","first-page":"2826","DOI":"10.1091\/mbc.02-05-0064","article-title":"Identification of the functional domains of yeast sorting nexins Vps5p and Vps17p","volume":"13","author":"Seaman","year":"2002","journal-title":"Mol. Biol. Cell"},{"key":"2021042521173111800_R47","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1083\/jcb.142.3.665","article-title":"A membrane coat complex essential for endosome-to-Golgi retrograde transport in yeast","volume":"142","author":"Seaman","year":"1998","journal-title":"J. Cell Biol."},{"key":"2021042521173111800_R48","doi-asserted-by":"crossref","first-page":"2371","DOI":"10.1242\/jcs.048686","article-title":"Membrane recruitment of the cargo-selective retromer subcomplex is catalysed by the small GTPase Rab7 and inhibited by the Rab-GAP TBC1D5","volume":"122","author":"Seaman","year":"2009","journal-title":"J. Cell Sci."},{"key":"2021042521173111800_R49","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1091\/mbc.e05-07-0682","article-title":"GMx33 associates with the trans-Golgi matrix in a dynamic manner and sorts within tubules exiting the Golgi","volume":"17","author":"Snyder","year":"2006","journal-title":"Mol. Biol. Cell."},{"key":"2021042521173111800_R50","doi-asserted-by":"crossref","first-page":"4694","DOI":"10.1091\/mbc.e08-03-0296","article-title":"Opposing activities of the SNX3-retromer complex and ESCRT proteins mediate regulated cargo sorting at a common endosome","volume":"19","author":"Strochlic","year":"2008","journal-title":"Mol. Biol. Cell."},{"key":"2021042521173111800_R51","doi-asserted-by":"crossref","first-page":"3805","DOI":"10.1093\/hmg\/ddp324","article-title":"The hereditary spastic paraplegia proteins NIPA1, spastin and spartin are inhibitors of mammalian BMP signalling","volume":"18","author":"Tsang","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"2021042521173111800_R52","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1086\/510782","article-title":"Mutations in the KIAA0196 gene at the SPG8 locus cause hereditary spastic paraplegia","volume":"80","author":"Valdmanis","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"2021042521173111800_R53","first-page":"153","article-title":"Retromer: multipurpose sorting and specialization in polarized transport","volume":"271","author":"Verges","year":"2008","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"2021042521173111800_R54","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1016\/j.yexcr.2008.12.004","article-title":"WAFL, a new protein involved in regulation of early endocytic transport at the intersection of actin and microtubule dynamics","volume":"315","author":"Viklund","year":"2009","journal-title":"Exp. Cell Res."},{"key":"2021042521173111800_R55","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1242\/jcs.03302","article-title":"A loss-of-function screen reveals SNX5 and SNX6 as potential components of the mammalian retromer","volume":"120","author":"Wassmer","year":"2007","journal-title":"J. Cell Sci."},{"key":"2021042521173111800_R56","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.devcel.2009.04.016","article-title":"The retromer coat complex coordinates endosomal sorting and dynein-mediated transport, with carrier recognition by the trans-Golgi network","volume":"17","author":"Wassmer","year":"2009","journal-title":"Dev. Cell"},{"key":"2021042521173111800_R57","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/nmeth.1322","article-title":"Universal sample preparation method for proteome analysis","volume":"6","author":"Wisniewski","year":"2009","journal-title":"Nat. Methods"},{"key":"2021042521173111800_R58","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1083\/jcb.200909063","article-title":"PtdIns4P recognition by Vps74\/GOLPH3 links PtdIns 4-kinase signaling to retrograde Golgi trafficking","volume":"187","author":"Wood","year":"2009","journal-title":"J. Cell Biol."},{"key":"2021042521173111800_R59","first-page":"963","article-title":"GMx33: a novel family of trans-Golgi proteins identified by proteomics","volume":"1","author":"Wu","year":"2000","journal-title":"Traffic"}],"container-title":["Journal of Cell Science"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/journals.biologists.com\/jcs\/article-pdf\/123\/21\/3703\/1489219\/3703.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/jcs\/article-pdf\/123\/21\/3703\/1489219\/3703.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,25]],"date-time":"2021-04-25T22:14:31Z","timestamp":1619388871000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/jcs\/article\/123\/21\/3703\/31410\/The-cargo-selective-retromer-complex-is-a"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,11,1]]},"references-count":59,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2010,11,1]]}},"URL":"https:\/\/doi.org\/10.1242\/jcs.071472","relation":{},"ISSN":["1477-9137","0021-9533"],"issn-type":[{"value":"1477-9137","type":"electronic"},{"value":"0021-9533","type":"print"}],"subject":[],"published":{"date-parts":[[2010,11,1]]}}}