{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T04:04:43Z","timestamp":1768968283705,"version":"3.49.0"},"reference-count":41,"publisher":"The Company of Biologists","issue":"2","license":[{"start":{"date-parts":[[2017,7,15]],"date-time":"2017-07-15T00:00:00Z","timestamp":1500076800000},"content-version":"vor","delay-in-days":181,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["STE2310\/1-1"],"award-info":[{"award-number":["STE2310\/1-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["089928"],"award-info":[{"award-number":["089928"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["086777"],"award-info":[{"award-number":["086777"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["093549"],"award-info":[{"award-number":["093549"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["31003A-166482\/1"],"award-info":[{"award-number":["31003A-166482\/1"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,1,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Retromer and the associated actin-polymerizing WASH complex are essential for the endocytic recycling of a wide range of integral membrane proteins. A hereditary Parkinson's-disease-causing point mutation (D620N) in the retromer subunit VPS35 perturbs retromer's association with the WASH complex and also with the uncharacterized protein ankyrin-repeat-domain-containing protein 50 (ANKRD50). Here, we firmly establish ANKRD50 as a new and essential component of the SNX27\u2013retromer\u2013WASH super complex. Depletion of ANKRD50 in HeLa or U2OS cells phenocopied the loss of endosome-to-cell-surface recycling of multiple transmembrane proteins seen upon suppression of SNX27, retromer or WASH-complex components. Mass-spectrometry-based quantification of the cell surface proteome of ANKRD50-depleted cells identified amino acid transporters of the SLC1A family, among them SLC1A4, as additional cargo molecules that depend on ANKRD50 and retromer for their endocytic recycling. Mechanistically, we show that ANKRD50 simultaneously engages multiple parts of the SNX27\u2013retromer\u2013WASH complex machinery in a direct and co-operative interaction network that is needed to efficiently recycle the nutrient transporters GLUT1 (also known as SLC2A1) and SLC1A4, and potentially many other surface proteins.<\/jats:p>","DOI":"10.1242\/jcs.196758","type":"journal-article","created":{"date-parts":[[2016,12,2]],"date-time":"2016-12-02T02:50:38Z","timestamp":1480647038000},"page":"382-395","source":"Crossref","is-referenced-by-count":48,"title":["Retromer- and WASH-dependent sorting of nutrient transporters requires a multivalent interaction network with ANKRD50"],"prefix":"10.1242","volume":"130","author":[{"given":"Arunas","family":"Kvainickas","sequence":"first","affiliation":[{"name":"Center for Biological Systems Analysis (ZBSA), Albert Ludwigs Universitaet Freiburg 1 , Habsburgerstrasse 49, Freiburg 79104 , Germany"},{"name":"Faculty of Biology 2 , Schaenzlestrasse 1, D-79104, Freiburg , Germany"}]},{"given":"Ana Jimenez","family":"Orgaz","sequence":"additional","affiliation":[{"name":"Center for Biological Systems Analysis (ZBSA), Albert Ludwigs Universitaet Freiburg 1 , Habsburgerstrasse 49, Freiburg 79104 , Germany"},{"name":"Faculty of Biology 2 , Schaenzlestrasse 1, D-79104, Freiburg , Germany"}]},{"given":"Heike","family":"N\u00e4gele","sequence":"additional","affiliation":[{"name":"Center for Biological Systems Analysis (ZBSA), Albert Ludwigs Universitaet Freiburg 1 , Habsburgerstrasse 49, Freiburg 79104 , Germany"},{"name":"Faculty of Biology 2 , Schaenzlestrasse 1, D-79104, Freiburg , Germany"}]},{"given":"Britta","family":"Diedrich","sequence":"additional","affiliation":[{"name":"Center for Biological Systems Analysis (ZBSA), Albert Ludwigs Universitaet Freiburg 1 , Habsburgerstrasse 49, Freiburg 79104 , Germany"},{"name":"Faculty of Biology 2 , Schaenzlestrasse 1, D-79104, Freiburg , Germany"}]},{"given":"Kate J.","family":"Heesom","sequence":"additional","affiliation":[{"name":"School of Biochemistry, Bristol University, University Walk 3 , Bristol BS81TD , UK"}]},{"given":"J\u00f6rn","family":"Dengjel","sequence":"additional","affiliation":[{"name":"Fribourg University 4 Department of Biology , , Chemin du Musee 10, Fribourg CH-1700 , Switzerland"}]},{"given":"Peter J.","family":"Cullen","sequence":"additional","affiliation":[{"name":"School of Biochemistry, Bristol University, University Walk 3 , Bristol BS81TD , UK"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1849-0506","authenticated-orcid":false,"given":"Florian","family":"Steinberg","sequence":"additional","affiliation":[{"name":"Center for Biological Systems Analysis (ZBSA), Albert Ludwigs Universitaet Freiburg 1 , Habsburgerstrasse 49, Freiburg 79104 , Germany"},{"name":"Faculty of Biology 2 , Schaenzlestrasse 1, D-79104, Freiburg , Germany"}]}],"member":"237","reference":[{"key":"2024061316330720900_JCS196758C1","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1038\/ncb2501","article-title":"Sorting nexin 17 prevents lysosomal degradation of beta(1) integrins by binding to the beta(1)-integrin tail","volume":"14","author":"Bottcher","year":"2012","journal-title":"Nat. Cell Biol."},{"key":"2024061316330720900_JCS196758C2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a016774","article-title":"Retromer: a master conductor of endosome sorting","volume":"6","author":"Burd","year":"2014","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"2024061316330720900_JCS196758C3","doi-asserted-by":"publisher","first-page":"1734","DOI":"10.1128\/MCB.01044-10","article-title":"Deficiency of sorting nexin 27 (SNX27) leads to growth retardation and elevated levels of N-methyl-D-aspartate receptor 2C (NR2C)","volume":"31","author":"Cai","year":"2011","journal-title":"Mol. Cell. Biol."},{"key":"2024061316330720900_JCS196758C4","doi-asserted-by":"publisher","first-page":"1367","DOI":"10.1091\/mbc.E15-12-0851","article-title":"Sorting nexin 27 couples PTHR trafficking to retromer for signal regulation in osteoblasts during bone growth","volume":"27","author":"Chan","year":"2016","journal-title":"Mol. Biol. Cell"},{"key":"2024061316330720900_JCS196758C5","doi-asserted-by":"publisher","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":"2024061316330720900_JCS196758C6","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1002\/cm.21069","article-title":"Regulation of integrin trafficking, cell adhesion, and cell migration by WASH and the Arp2\/3 complex","volume":"69","author":"Duleh","year":"2012","journal-title":"Cytoskeleton"},{"key":"2024061316330720900_JCS196758C7","doi-asserted-by":"publisher","first-page":"1467","DOI":"10.1523\/JNEUROSCI.2272-11.2012","article-title":"Retromer binds the FANSHY sorting motif in SorLA to regulate amyloid precursor protein sorting and processing","volume":"32","author":"Fjorback","year":"2012","journal-title":"J. Neurosci."},{"key":"2024061316330720900_JCS196758C8","doi-asserted-by":"publisher","first-page":"E3604","DOI":"10.1073\/pnas.1410552111","article-title":"A unique PDZ domain and arrestin-like fold interaction reveals mechanistic details of endocytic recycling by SNX27-retromer","volume":"111","author":"Gallon","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2024061316330720900_JCS196758C9","doi-asserted-by":"publisher","first-page":"E643","DOI":"10.1073\/pnas.1216229110","article-title":"Structural basis for endosomal trafficking of diverse transmembrane cargos by PX-FERM proteins","volume":"110","author":"Ghai","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2024061316330720900_JCS196758C10","doi-asserted-by":"publisher","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":"2024061316330720900_JCS196758C11","doi-asserted-by":"publisher","first-page":"3215","DOI":"10.1091\/mbc.E12-02-0101","article-title":"Trafficking defects in WASH-knockout fibroblasts originate from collapsed endosomal and lysosomal networks","volume":"23","author":"Gomez","year":"2012","journal-title":"Mol. Biol. Cell"},{"key":"2024061316330720900_JCS196758C12","doi-asserted-by":"publisher","first-page":"3703","DOI":"10.1242\/jcs.071472","article-title":"The cargo-selective retromer complex is a recruiting hub for protein complexes that regulate endosomal tubule dynamics","volume":"123","author":"Harbour","year":"2010","journal-title":"J. Cell Sci."},{"key":"2024061316330720900_JCS196758C13","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1042\/BJ20111761","article-title":"Recruitment of the endosomal WASH complex is mediated by the extended \u2018tail\u2019 of Fam21 binding to the retromer protein Vps35","volume":"442","author":"Harbour","year":"2012","journal-title":"Biochem. J."},{"key":"2024061316330720900_JCS196758C14","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1073\/pnas.1316482111","article-title":"A mechanism for retromer endosomal coat complex assembly with cargo","volume":"111","author":"Harrison","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2024061316330720900_JCS196758C15","doi-asserted-by":"publisher","first-page":"11840","DOI":"10.1073\/pnas.1412415111","article-title":"Sorting Nexin 27 regulates basal and activity-dependent trafficking of AMPARs","volume":"111","author":"Hussain","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2024061316330720900_JCS196758C16","doi-asserted-by":"publisher","first-page":"10442","DOI":"10.1073\/pnas.0913293107","article-title":"WASH and WAVE actin regulators of the Wiskott-Aldrich syndrome protein (WASP) family are controlled by analogous structurally related complexes","volume":"107","author":"Jia","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2024061316330720900_JCS196758C17","doi-asserted-by":"publisher","first-page":"2352","DOI":"10.1091\/mbc.E11-12-1059","article-title":"Multiple repeat elements within the FAM21 tail link the WASH actin regulatory complex to the retromer","volume":"23","author":"Jia","year":"2012","journal-title":"Mol. Biol. Cell"},{"key":"2024061316330720900_JCS196758C18","doi-asserted-by":"publisher","first-page":"1511","DOI":"10.1038\/nprot.2012.085","article-title":"Template-based protein structure modeling using the RaptorX web server","volume":"7","author":"Kallberg","year":"2012","journal-title":"Nat. Protoc."},{"key":"2024061316330720900_JCS196758C19","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1083\/jcb.201004060","article-title":"SNX27 mediates PDZ-directed sorting from endosomes to the plasma membrane","volume":"190","author":"Lauffer","year":"2010","journal-title":"J. Cell Biol."},{"key":"2024061316330720900_JCS196758C20","doi-asserted-by":"publisher","first-page":"10939","DOI":"10.1038\/ncomms10939","article-title":"FAM21 directs SNX27-retromer cargoes to the plasma membrane by preventing transport to the Golgi apparatus","volume":"7","author":"Lee","year":"2016","journal-title":"Nat. Commun."},{"key":"2024061316330720900_JCS196758C21","doi-asserted-by":"publisher","first-page":"3176","DOI":"10.1038\/ncomms4176","article-title":"A role for sorting nexin 27 in AMPA receptor trafficking","volume":"5","author":"Loo","year":"2014","journal-title":"Nat. Commun."},{"key":"2024061316330720900_JCS196758C22","doi-asserted-by":"publisher","first-page":"10986","DOI":"10.1074\/jbc.M115.697045","article-title":"Actin-Sorting Nexin 27 (SNX27)-retromer complex mediates rapid parathyroid hormone receptor recycling","volume":"291","author":"McGarvey","year":"2016","journal-title":"J. Biol. Chem."},{"key":"2024061316330720900_JCS196758C23","doi-asserted-by":"publisher","first-page":"4940","DOI":"10.1242\/jcs.156299","article-title":"Identification of molecular heterogeneity in SNX27-retromer-mediated endosome-to-plasma-membrane recycling","volume":"127","author":"McGough","year":"2014","journal-title":"J. Cell Sci."},{"key":"2024061316330720900_JCS196758C24","doi-asserted-by":"publisher","first-page":"1670","DOI":"10.1016\/j.cub.2014.06.024","article-title":"Retromer binding to FAM21 and the WASH complex is perturbed by the parkinson disease-linked VPS35(D620N) mutation","volume":"24","author":"McGough","year":"2014","journal-title":"Curr. Biol."},{"key":"2024061316330720900_JCS196758C25","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2014.07.004","article-title":"Retromer binding to FAM21 and the WASH complex is perturbed by the parkinson disease-linked VPS35(D620N) mutation (vol 24, pg 1670, 2014)","volume":"24","author":"McGough","year":"2014","journal-title":"Curr. Biol."},{"key":"2024061316330720900_JCS196758C26","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1091\/mbc.E14-06-1073","article-title":"COMMD1 is linked to the WASH complex and regulates endosomal trafficking of the copper transporter ATP7A","volume":"26","author":"Phillips-Krawczak","year":"2015","journal-title":"Mol. Biol. Cell"},{"key":"2024061316330720900_JCS196758C27","doi-asserted-by":"publisher","first-page":"958","DOI":"10.1128\/MCB.01288-12","article-title":"WASH knockout T cells demonstrate defective receptor trafficking, proliferation, and effector function","volume":"33","author":"Piotrowski","year":"2013","journal-title":"Mol. Cell. Biol."},{"key":"2024061316330720900_JCS196758C28","doi-asserted-by":"publisher","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":"2024061316330720900_JCS196758C29","doi-asserted-by":"publisher","first-page":"4693","DOI":"10.1242\/jcs.103440","article-title":"The retromer complex - endosomal protein recycling and beyond","volume":"125","author":"Seaman","year":"2012","journal-title":"J. Cell Sci."},{"key":"2024061316330720900_JCS196758C30","doi-asserted-by":"publisher","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":"2024061316330720900_JCS196758C31","doi-asserted-by":"publisher","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":"2024061316330720900_JCS196758C32","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1083\/jcb.201111121","article-title":"SNX17 protects integrins from degradation by sorting between lysosomal and recycling pathways","volume":"197","author":"Steinberg","year":"2012","journal-title":"J. Cell Biol."},{"key":"2024061316330720900_JCS196758C33","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1038\/ncb2721","article-title":"A global analysis of SNX27-retromer assembly and cargo specificity reveals a function in glucose and metal ion transport","volume":"15","author":"Steinberg","year":"2013","journal-title":"Nat. Cell Biol."},{"key":"2024061316330720900_JCS196758C34","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1242\/jcs.060574","article-title":"Retromer-mediated direct sorting is required for proper endosomal recycling of the mammalian iron transporter DMT1","volume":"123","author":"Tabuchi","year":"2010","journal-title":"J. Cell Sci."},{"key":"2024061316330720900_JCS196758C35","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1038\/ncb2252","article-title":"SNX27 mediates retromer tubule entry and endosome-to-plasma membrane trafficking of signalling receptors","volume":"13","author":"Temkin","year":"2011","journal-title":"Nat. Cell Biol."},{"key":"2024061316330720900_JCS196758C36","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/j.ajhg.2011.06.001","article-title":"VPS35 mutations in Parkinson disease","volume":"89","author":"Vilarino-Guell","year":"2011","journal-title":"Am. J. Hum. Genet."},{"key":"2024061316330720900_JCS196758C37","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1038\/nm.3117","article-title":"Loss of sorting nexin 27 contributes to excitatory synaptic dysfunction by modulating glutamate receptor recycling in Down's syndrome","volume":"19","author":"Wang","year":"2013","journal-title":"Nat. Med."},{"key":"2024061316330720900_JCS196758C38","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1083\/jcb.201105109","article-title":"VPS35 haploinsufficiency increases Alzheimer's disease neuropathology","volume":"195","author":"Wen","year":"2011","journal-title":"J. Cell Biol."},{"key":"2024061316330720900_JCS196758C39","doi-asserted-by":"publisher","first-page":"3828","DOI":"10.1038\/ncomms4828","article-title":"Mutation in VPS35 associated with Parkinson's disease impairs WASH complex association and inhibits autophagy","volume":"5","author":"Zavodszky","year":"2014","journal-title":"Nat. Commun."},{"key":"2024061316330720900_JCS196758C40","doi-asserted-by":"publisher","first-page":"3753","DOI":"10.1242\/jcs.080986","article-title":"The Arp2\/3 activator WASH regulates alpha5beta1-integrin-mediated invasive migration","volume":"124","author":"Zech","year":"2011","journal-title":"J. Cell Sci."},{"key":"2024061316330720900_JCS196758C41","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1016\/j.ajhg.2011.06.008","article-title":"A mutation in VPS35, encoding a subunit of the retromer complex, causes late-onset Parkinson disease","volume":"89","author":"Zimprich","year":"2011","journal-title":"Am. J. Hum. Genet."}],"container-title":["Journal of Cell Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1242\/jcs.196758","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/jcs\/article-pdf\/130\/2\/382\/3497029\/jcs196758.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/jcs\/article-pdf\/doi\/10.1242\/jcs.196758\/2057113\/jcs196758.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/jcs\/article-pdf\/130\/2\/382\/3497029\/jcs196758.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T16:43:52Z","timestamp":1718297032000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/jcs\/article\/130\/2\/382\/56522\/Retromer-and-WASH-dependent-sorting-of-nutrient"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,1,15]]},"references-count":41,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2017,1,15]]}},"URL":"https:\/\/doi.org\/10.1242\/jcs.196758","relation":{},"ISSN":["1477-9137","0021-9533"],"issn-type":[{"value":"1477-9137","type":"electronic"},{"value":"0021-9533","type":"print"}],"subject":[],"published":{"date-parts":[[2017,1,15]]}}}