title: ACBD5 and VAPB mediate membrane associations between peroxisomes and the ER.
abstract: Peroxisomes (POs) and the endoplasmic reticulum (ER) cooperate in cellular lipid metabolism and form tight structural associations, which were first observed in ultrastructural studies decades ago. PO-ER 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-binding 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-VAPB interaction regulates PO-ER associations. Moreover, we demonstrate that loss of PO-ER association perturbs PO membrane expansion and increases PO movement. Our findings reveal the first molecular mechanism for establishing PO-ER associations in mammalian cells and report a new function for ACBD5 in PO-ER tethering.
authors.affiliation: Biosciences, University of Exeter, Exeter EX4 4QD, England, UK.
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Costello
authors.affiliation: Biosciences, University of Exeter, Exeter EX4 4QD, England, UK.
authors.forename: Inês G
authors.identifier: http://orcid.org/0000-0003-4669-985X
authors.initials: IG
authors.lastname: Castro
authors.affiliation: Biosciences, University of Exeter, Exeter EX4 4QD, England, UK.
authors.forename: Christian
authors.initials: C
authors.lastname: Hacker
authors.affiliation: Biosciences, University of Exeter, Exeter EX4 4QD, England, UK.
authors.forename: Tina A
authors.initials: TA
authors.lastname: Schrader
authors.affiliation: Biosciences, University of Exeter, Exeter EX4 4QD, England, UK.
authors.forename: Jeremy
authors.identifier: http://orcid.org/0000-0002-8099-8776
authors.initials: J
authors.lastname: Metz
authors.affiliation: Max Planck Institute for Molecular Biomedicine, 48149 Muenster, Germany.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Zeuschner
authors.affiliation: Biosciences, University of Exeter, Exeter EX4 4QD, England, UK.
authors.forename: Afsoon S
authors.identifier: http://orcid.org/0000-0002-1721-5476
authors.initials: AS
authors.lastname: Azadi
authors.affiliation: Biosciences, University of Exeter, Exeter EX4 4QD, England, UK.
authors.forename: Luis F
authors.identifier: http://orcid.org/0000-0002-2135-5148
authors.initials: LF
authors.lastname: Godinho
authors.affiliation: Institute for Clinical Chemistry, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany.
authors.forename: Victor
authors.identifier: http://orcid.org/0000-0002-9752-6943
authors.initials: V
authors.lastname: Costina
authors.affiliation: Institute for Clinical Chemistry, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Findeisen
authors.affiliation: Institute of Neuroanatomy, Center for Biomedicine and Medical Technology Mannheim, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany.
authors.forename: Andreas
authors.identifier: http://orcid.org/0000-0002-3315-1724
authors.initials: A
authors.lastname: Manner
authors.affiliation: Institute of Neuroanatomy, Center for Biomedicine and Medical Technology Mannheim, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany.
authors.forename: Markus
authors.identifier: http://orcid.org/0000-0001-8881-0902
authors.initials: M
authors.lastname: Islinger
authors.affiliation: Biosciences, University of Exeter, Exeter EX4 4QD, England, UK M.Schrader@exeter.ac.uk.
authors.forename: Michael
authors.identifier: http://orcid.org/0000-0003-2146-0535
authors.initials: M
authors.lastname: Schrader
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000648:ultrastructure; D056945:Hep G2 Cells; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism* / Q000648:ultrastructure; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D009068:Movement; D020675:Peroxisomes / Q000378:metabolism* / Q000648:ultrastructure; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D019108:Tight Junctions / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C548478:ACBD5 protein, human; D048868:Adaptor Proteins, Signal Transducing; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; C496748:VAPB protein, human; D033921:Vesicular Transport Proteins