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PMID: 20098723 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

Neuron specific Rab4 effector GRASP-1 coordinates membrane specialization and maturation of recycling endosomes.

PLoS biology ·Vol. 8 ·No. 1 ·2010-01-19 ·Pages e1000283

Hoogenraad CC, Popa I, Futai K, Martinez-Sanchez E, Sanchez-Martinez E, Wulf PS, van Vlijmen T, Dortland BR, Oorschot V, Govers R, Monti M, Heck AJ, Sheng M, Klumperman J, Rehmann H, Jaarsma D, Kapitein LC, van der Sluijs P

Abstract

The endosomal pathway in neuronal dendrites is essential for membrane receptor trafficking and proper synaptic function and plasticity. However, the molecular mechanisms that organize specific endocytic trafficking routes are poorly understood. Here, we identify GRIP-associated protein-1 (GRASP-1) as a neuron-specific effector of Rab4 and key component of the molecular machinery that coordinates recycling endosome maturation in dendrites. We show that GRASP-1 is necessary for AMPA receptor recycling, maintenance of spine morphology, and synaptic plasticity. At the molecular level, GRASP-1 segregates Rab4 from EEA1/Neep21/Rab5-positive early endosomal membranes and coordinates the coupling to Rab11-labelled recycling endosomes by interacting with the endosomal SNARE syntaxin 13. We propose that GRASP-1 connects early and late recycling endosomal compartments by forming a molecular bridge between Rab-specific membrane domains and the endosomal SNARE machinery. The data uncover a new mechanism to achieve specificity and directionality in neuronal membrane receptor trafficking.

MeSH Terms
Animals Biological Transport COS Cells Carrier Proteins/analysis,metabolism,physiology Chlorocebus aethiops Dendrites/metabolism,ultrastructure Endosomes/metabolism Escherichia coli/genetics HeLa Cells Humans Intracellular Membranes/metabolism,physiology Mice Neuronal Plasticity Qa-SNARE Proteins/metabolism Rats Receptors, Glutamate/metabolism Swine rab4 GTP-Binding Proteins/analysis,metabolism,physiology
Chemicals
Carrier Proteins Qa-SNARE Proteins Receptors, Glutamate rab4 GTP-Binding Proteins
Authors & Affiliations
18 authors, click to expand affiliations / ORCID
Hoogenraad Casper C
Department of Neuroscience, Erasmus Medical Center, Rotterdam, The Netherlands. c.hoogenraad@erasmusmc.nl
Popa Ioana
Futai Kensuke
Martinez-Sanchez Emma
Sanchez-Martinez Emma
Wulf Phebe S
van Vlijmen Thijs
Dortland Bjorn R
Oorschot Viola
Govers Roland
Monti Maria
Heck Albert J R
Sheng Morgan
Klumperman Judith
Rehmann Holger
Jaarsma Dick
Kapitein Lukas C
van der Sluijs Peter
Conflict of Interest

The authors have declared that no competing interests exist.

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Article Info
Journal
PLoS biology
Abbr.
PLoS Biol
ISSN
1545-7885
Published
2010-01-19
Epub
2010-00-19
Pages
e1000283
Language
English
Region
United States
NLM ID
101183755
PMCID
PMC2808209
Subset
IM
Corrections
ErratumIn
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