Neuron specific Rab4 effector GRASP-1 coordinates membrane specialization and maturation of recycling endosomes.
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.
Hoogenraad
Casper C
CC
Department of Neuroscience, Erasmus Medical Center, Rotterdam, The Netherlands. c.hoogenraad@erasmusmc.nl
Popa
Ioana
I
Futai
Kensuke
K
Martinez-Sanchez
Emma
E
Sanchez-Martinez
Emma
E
Wulf
Phebe S
PS
van Vlijmen
Thijs
T
Dortland
Bjorn R
BR
Oorschot
Viola
V
Govers
Roland
R
Monti
Maria
M
Heck
Albert J R
AJ
Sheng
Morgan
M
Klumperman
Judith
J
Rehmann
Holger
H
Jaarsma
Dick
D
Kapitein
Lukas C
LC
van der Sluijs
Peter
P
D000818:Animals; D001692:Biological Transport; D019556:COS Cells; D002352:Carrier Proteins / Q000032:analysis / Q000378:metabolism / Q000502:physiology; D002522:Chlorocebus aethiops; D003712:Dendrites / Q000378:metabolism* / Q000648:ultrastructure; D011992:Endosomes / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism / Q000502:physiology; D051379:Mice; D009473:Neuronal Plasticity; D050765:Qa-SNARE Proteins / Q000378:metabolism; D051381:Rats; D017470:Receptors, Glutamate / Q000378:metabolism; D013552:Swine; D020695:rab4 GTP-Binding Proteins / Q000032:analysis / Q000378:metabolism* / Q000502:physiology
D002352:Carrier Proteins; D050765:Qa-SNARE Proteins; D017470:Receptors, Glutamate; D020695:rab4 GTP-Binding Proteins