title: Neuron specific Rab4 effector GRASP-1 coordinates membrane specialization and maturation of recycling endosomes.
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.
authors.affiliation: Department of Neuroscience, Erasmus Medical Center, Rotterdam, The Netherlands. c.hoogenraad@erasmusmc.nl
authors.forename: Casper C
authors.initials: CC
authors.lastname: Hoogenraad
authors.forename: Ioana
authors.initials: I
authors.lastname: Popa
authors.forename: Kensuke
authors.initials: K
authors.lastname: Futai
authors.forename: Emma
authors.initials: E
authors.lastname: Martinez-Sanchez
authors.forename: Emma
authors.initials: E
authors.lastname: Sanchez-Martinez
authors.forename: Phebe S
authors.initials: PS
authors.lastname: Wulf
authors.forename: Thijs
authors.initials: T
authors.lastname: van Vlijmen
authors.forename: Bjorn R
authors.initials: BR
authors.lastname: Dortland
authors.forename: Viola
authors.initials: V
authors.lastname: Oorschot
authors.forename: Roland
authors.initials: R
authors.lastname: Govers
authors.forename: Maria
authors.initials: M
authors.lastname: Monti
authors.forename: Albert J R
authors.initials: AJ
authors.lastname: Heck
authors.forename: Morgan
authors.initials: M
authors.lastname: Sheng
authors.forename: Judith
authors.initials: J
authors.lastname: Klumperman
authors.forename: Holger
authors.initials: H
authors.lastname: Rehmann
authors.forename: Dick
authors.initials: D
authors.lastname: Jaarsma
authors.forename: Lukas C
authors.initials: LC
authors.lastname: Kapitein
authors.forename: Peter
authors.initials: P
authors.lastname: van der Sluijs
mesh_terms: 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
chemical_list: D002352:Carrier Proteins; D050765:Qa-SNARE Proteins; D017470:Receptors, Glutamate; D020695:rab4 GTP-Binding Proteins