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J Cell Biol. 2017 Feb;216(2):331-342. doi: 10.1083/jcb.201607055. Epub 2017 Jan 20.

ACBD5 and VAPB mediate membrane associations between peroxisomes and the ER.

Author information

1
Biosciences, University of Exeter, Exeter EX4 4QD, England, UK.
2
Max Planck Institute for Molecular Biomedicine, 48149 Muenster, Germany.
3
Institute for Clinical Chemistry, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany.
4
Institute of Neuroanatomy, Center for Biomedicine and Medical Technology Mannheim, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany.
5
Biosciences, University of Exeter, Exeter EX4 4QD, England, UK M.Schrader@exeter.ac.uk.

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.

PMID:
28108524
PMCID:
PMC5294785
DOI:
10.1083/jcb.201607055
[Indexed for MEDLINE]
Free PMC Article

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