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PO\u2013ER associations have been suggested to impact on a diverse number of physiological processes, including lipid metabolism, phospholipid exchange, metabolite transport, signaling, and PO biogenesis. Despite their fundamental importance to cell metabolism, the mechanisms by which regions of the ER become tethered to POs are unknown, in particular in mammalian cells. Here, we identify the PO membrane protein acyl-coenzyme A\u2013binding domain protein 5 (ACBD5) as a binding partner for the resident ER protein vesicle-associated membrane protein-associated protein B (VAPB). We show that ACBD5\u2013VAPB interaction regulates PO\u2013ER associations. Moreover, we demonstrate that loss of PO\u2013ER association perturbs PO membrane expansion and increases PO movement. Our findings reveal the first molecular mechanism for establishing PO\u2013ER associations in mammalian cells and report a new function for ACBD5 in PO\u2013ER tethering.<\/jats:p>","DOI":"10.1083\/jcb.201607055","type":"journal-article","created":{"date-parts":[[2017,1,21]],"date-time":"2017-01-21T10:10:19Z","timestamp":1484993419000},"page":"331-342","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":234,"title":["ACBD5 and VAPB mediate membrane associations between peroxisomes and the ER"],"prefix":"10.1083","volume":"216","author":[{"given":"Joseph L.","family":"Costello","sequence":"first","affiliation":[{"name":"Biosciences, University of Exeter, Exeter EX4 4QD, England, UK 1"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4669-985X","authenticated-orcid":true,"given":"In\u00eas G.","family":"Castro","sequence":"additional","affiliation":[{"name":"Biosciences, University of Exeter, Exeter EX4 4QD, England, UK 1"}]},{"given":"Christian","family":"Hacker","sequence":"additional","affiliation":[{"name":"Biosciences, University of Exeter, Exeter EX4 4QD, England, UK 1"}]},{"given":"Tina A.","family":"Schrader","sequence":"additional","affiliation":[{"name":"Biosciences, University of Exeter, Exeter EX4 4QD, England, UK 1"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8099-8776","authenticated-orcid":true,"given":"Jeremy","family":"Metz","sequence":"additional","affiliation":[{"name":"Biosciences, University of Exeter, Exeter EX4 4QD, England, UK 1"}]},{"given":"Dagmar","family":"Zeuschner","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Molecular Biomedicine, 48149 Muenster, Germany 2"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1721-5476","authenticated-orcid":true,"given":"Afsoon S.","family":"Azadi","sequence":"additional","affiliation":[{"name":"Biosciences, University of Exeter, Exeter EX4 4QD, England, UK 1"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2135-5148","authenticated-orcid":true,"given":"Luis F.","family":"Godinho","sequence":"additional","affiliation":[{"name":"Biosciences, University of Exeter, Exeter EX4 4QD, England, UK 1"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9752-6943","authenticated-orcid":true,"given":"Victor","family":"Costina","sequence":"additional","affiliation":[{"name":"Institute for Clinical Chemistry, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany 3"}]},{"given":"Peter","family":"Findeisen","sequence":"additional","affiliation":[{"name":"Institute for Clinical Chemistry, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany 3"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3315-1724","authenticated-orcid":true,"given":"Andreas","family":"Manner","sequence":"additional","affiliation":[{"name":"Institute of Neuroanatomy, Center for Biomedicine and Medical Technology Mannheim, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany 4"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8881-0902","authenticated-orcid":true,"given":"Markus","family":"Islinger","sequence":"additional","affiliation":[{"name":"Institute of Neuroanatomy, Center for Biomedicine and Medical Technology Mannheim, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany 4"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2146-0535","authenticated-orcid":true,"given":"Michael","family":"Schrader","sequence":"additional","affiliation":[{"name":"Biosciences, University of Exeter, Exeter EX4 4QD, England, UK 1"}]}],"member":"291","published-online":{"date-parts":[[2017,1,20]]},"reference":[{"key":"2023072309114580400_bib1","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1101\/gr.144105.112","article-title":"Autozygome-guided exome sequencing in retinal dystrophy patients reveals pathogenetic mutations and novel candidate disease genes","volume":"23","author":"Abu-Safieh","year":"2013","journal-title":"Genome Res."},{"key":"2023072309114580400_bib2","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1007\/978-1-62703-056-4_24","article-title":"Cytochemical detection of peroxisomes and mitochondria","volume":"931","author":"Bonekamp","year":"2013","journal-title":"Methods Mol. 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