Rab35 GTPase Triggers Switch-like Recruitment of the Lowe Syndrome Lipid Phosphatase OCRL on Newborn Endosomes.
Current Biology. 2016-01-01; 26(1): 120-128
DOI: 10.1016/j.cub.2015.11.040
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1. Curr Biol. 2016 Jan 11;26(1):120-8. doi: 10.1016/j.cub.2015.11.040. Epub 2015 Dec
24.
Rab35 GTPase Triggers Switch-like Recruitment of the Lowe Syndrome Lipid
Phosphatase OCRL on Newborn Endosomes.
Cauvin C(1), Rosendale M(2), Gupta-Rossi N(3), Rocancourt M(3), Larraufie P(3),
Salomon R(4), Perrais D(5), Echard A(6).
Author information:
(1)Membrane Traffic and Cell Division Lab, Cell Biology and Infection Department,
Institut Pasteur, 25-28 Rue du Dr. Roux, 75724 Paris Cedex 15, France; Centre
National de la Recherche Scientifique UMR3691, 75015 Paris, France; Institut de
Formation Doctorale, Sorbonne Universités and Université Pierre et Marie Curie,
Université Paris 06, 75252 Paris, France.
(2)University of Bordeaux, 33000 Bordeaux, France; Centre National de la
Recherche Scientifique, Interdisciplinary Institute for Neuroscience, UMR 5297,
33000 Bordeaux, France.
(3)Membrane Traffic and Cell Division Lab, Cell Biology and Infection Department,
Institut Pasteur, 25-28 Rue du Dr. Roux, 75724 Paris Cedex 15, France; Centre
National de la Recherche Scientifique UMR3691, 75015 Paris, France.
(4)Service de Néphrologie Pédiatrique, AP-HP Hôpital Necker, INSERM U983, 75015
Paris, France.
(5)University of Bordeaux, 33000 Bordeaux, France; Centre National de la
Recherche Scientifique, Interdisciplinary Institute for Neuroscience, UMR 5297,
33000 Bordeaux, France. Electronic address: .
(6)Membrane Traffic and Cell Division Lab, Cell Biology and Infection Department,
Institut Pasteur, 25-28 Rue du Dr. Roux, 75724 Paris Cedex 15, France; Centre
National de la Recherche Scientifique UMR3691, 75015 Paris, France. Electronic
address: .
Phosphoinositide (PtdIns) homeostasis requires a tight spatial and temporal
regulation during the endocytic process [1]. Indeed, PtdIns(4,5)P2 plays a
crucial role in endocytosis by controlling clathrin-coated pit formation, whereas
its conversion into PtdIns4P right after scission of clathrin-coated vesicles
(CCVs) is essential for successful uncoating and cargo sorting [1-6]. In
non-neuronal cells, endosomal PtdIns(4,5)P2 hydrolysis critically relies on
the lipid phosphatase OCRL [7-9], the inactivation of which causes the
Oculo-Cerebro-Renal syndrome of Lowe [10, 11]. To understand the coupling between
PtdIns(4,5)P2 hydrolysis and endosome formation, a key issue is thus to unravel
the mechanism by which OCRL is recruited on CCVs precisely after their scission
from the plasma membrane. Here we found that the Rab35 GTPase, which plays a
fundamental but poorly understood role in endosomal trafficking after cargo
internalization [12-21], directly recruits the OCRL phosphatase immediately after
scission of the CCVs. Consistent with Rab35 and OCRL acting together, depletion
of either Rab35 or OCRL leads to retention of internalized receptors such as the
endogenous cation-independent mannose-6-phosphate receptor (CI-MPR) in peripheral
clathrin-positive endosomes that display abnormal association with PtdIns(4,5)P2-
and actin-binding proteins. Remarkably, Rab35 loading on CCVs rapidly follows the
recruitment of the AP2-binding Rab35 GEF/activator DENND1A (connecdenn 1) and the
disappearance of the Rab35 GAP/inhibitor EPI64B. We propose that the precise
spatial and temporal activation of Rab35 acts as a major switch for OCRL
recruitment on newborn endosomes, post-scission PtdIns(4,5)P2 hydrolysis, and
subsequent endosomal trafficking.
Copyright © 2016 Elsevier Ltd. All rights reserved.
DOI: 10.1016/j.cub.2015.11.040
PMID: 26725203 [Indexed for MEDLINE]