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OCRL1 engages with the F-BAR protein pacsin 2 to promote biogenesis of membrane-trafficking intermediates

Title: OCRL1 engages with the F-BAR protein pacsin 2 to promote biogenesis of membrane-trafficking intermediates
Authors: Billcliff, PG
Noakes, CJ
Mehta, ZB
Yan, G
Mak, L
Woscholski, R
Lowe, M
Item Type: Journal Article
Abstract: Mutation of the inositol 5-phosphatase OCRL1 causes Lowe syndrome and Dent-2 disease. Loss of OCRL1 function perturbs several cellular processes, including membrane traffic, but the underlying mechanisms remain poorly defined. Here we show that OCRL1 is part of the membrane-trafficking machinery operating at the trans-Golgi network (TGN)/endosome interface. OCRL1 interacts via IPIP27A with the F-BAR protein pacsin 2. OCRL1 and IPIP27A localize to mannose 6-phosphate receptor (MPR)–containing trafficking intermediates, and loss of either protein leads to defective MPR carrier biogenesis at the TGN and endosomes. OCRL1 5-phosphatase activity, which is membrane curvature sensitive, is stimulated by IPIP27A-mediated engagement of OCRL1 with pacsin 2 and promotes scission of MPR-containing carriers. Our data indicate a role for OCRL1, via IPIP27A, in regulating the formation of pacsin 2–dependent trafficking intermediates and reveal a mechanism for coupling PtdIns(4,5)P2 hydrolysis with carrier biogenesis on endomembranes.
Issue Date: 28-Oct-2015
Date of Acceptance: 23-Oct-2015
URI: http://hdl.handle.net/10044/1/39416
DOI: https://dx.doi.org/10.1091/mbc.E15-06-0329
ISSN: 1939-4586
Publisher: American Society for Cell Biology
Start Page: 90
End Page: 107
Journal / Book Title: Molecular Biology of the Cell
Volume: 27
Issue: 1
Copyright Statement: © 2016 Billcliff, Noakes, Mehta, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/ licenses/by-nc-sa/3.0)
Sponsor/Funder: Engineering & Physical Science Research Council (EPSRC)
The Lowe Syndrome Trust
Funder's Grant Number: EP/K039946/1
IC/ICAP/2012
Keywords: Science & Technology
Life Sciences & Biomedicine
Cell Biology
TRANS-GOLGI NETWORK
MEDIATES RETROGRADE TRANSPORT
MANNOSE 6-PHOSPHATE RECEPTOR
LOWE-SYNDROME
OCULOCEREBRORENAL SYNDROME
SUBCELLULAR-LOCALIZATION
PHYSIOLOGICAL FUNCTIONS
ENDOCYTIC PROTEINS
CELL REGULATION
ACTIN DYNAMICS
Developmental Biology
06 Biological Sciences
11 Medical And Health Sciences
Publication Status: Published
Appears in Collections:Chemistry
Biological and Biophysical Chemistry
Faculty of Medicine
Faculty of Natural Sciences



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