{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T02:22:11Z","timestamp":1791339731866,"version":"4.3.1"},"reference-count":221,"publisher":"The Company of Biologists","issue":"10","license":[{"start":{"date-parts":[[2019,5,15]],"date-time":"2019-05-15T00:00:00Z","timestamp":1557878400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["40-00812-98-16006"],"award-info":[{"award-number":["40-00812-98-16006"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,5,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Multisubunit tethering complexes (MTCs) are multitasking hubs that form a link between membrane fusion, organelle motility and signaling. CORVET, CHEVI and HOPS are MTCs of the endo-lysosomal system. They regulate the major membrane flows required for endocytosis, lysosome biogenesis, autophagy and phagocytosis. In addition, individual subunits control complex-independent transport of specific cargoes and exert functions beyond tethering, such as attachment to microtubules and SNARE activation. Mutations in CHEVI subunits lead to arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome, while defects in CORVET and, particularly, HOPS are associated with neurodegeneration, pigmentation disorders, liver malfunction and various forms of cancer. Diseases and phenotypes, however, vary per affected subunit and a concise overview of MTC protein function and associated human pathologies is currently lacking. Here, we provide an integrated overview on the cellular functions and pathological defects associated with CORVET, CHEVI or HOPS proteins, both with regard to their complexes and as individual subunits. The combination of these data provides novel insights into how mutations in endo-lysosomal proteins lead to human pathologies.<\/jats:p>","DOI":"10.1242\/jcs.189134","type":"journal-article","created":{"date-parts":[[2019,5,15]],"date-time":"2019-05-15T15:15:46Z","timestamp":1557933346000},"source":"Crossref","is-referenced-by-count":130,"title":["CORVET, CHEVI and HOPS \u2013 multisubunit tethers of the endo-lysosomal system in health and disease"],"prefix":"10.1242","volume":"132","author":[{"given":"Jan","family":"van der Beek","sequence":"first","affiliation":[{"name":"Center for Molecular Medicine, University Medical Center Utrecht, Institute for Biomembranes, Utrecht University Section Cell Biology , , Utrecht 3584 CX , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caspar","family":"Jonker","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine, University Medical Center Utrecht, Institute for Biomembranes, Utrecht University Section Cell Biology , , Utrecht 3584 CX , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reini","family":"van der Welle","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine, University Medical Center Utrecht, Institute for Biomembranes, Utrecht University Section Cell Biology , , Utrecht 3584 CX , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nalan","family":"Liv","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine, University Medical Center Utrecht, Institute for Biomembranes, Utrecht University Section Cell Biology , , Utrecht 3584 CX , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4835-6228","authenticated-orcid":false,"given":"Judith","family":"Klumperman","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine, University Medical Center Utrecht, Institute for Biomembranes, Utrecht University Section Cell Biology , , Utrecht 3584 CX , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2019,5,15]]},"reference":[{"key":"2024061318141824800_JCS189134C1","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1097\/00019605-200510000-00005","article-title":"Arthrogryposis, renal tubular acidosis and cholestasis (ARC) syndrome: two new cases and review","volume":"14","author":"Abu-Sa'Da","year":"2005","journal-title":"Clin. 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