Article abstract
Nature Neuroscience 12, 1011 - 1019 (2009)
Published online: 20 July 2009 | doi:10.1038/nn.2362
SAP97 and CASK mediate sorting of NMDA receptors through a previously unknown secretory pathway
Okunola Jeyifous1, Clarissa L Waites1, Christian G Specht1, Sho Fujisawa2, Manja Schubert3, Eric I Lin4, John Marshall5, Chiye Aoki2, Tharani de Silva3, Johanna M Montgomery3, Craig C Garner1,6 & William N Green4,6
Abstract
Synaptic plasticity is dependent on the differential sorting, delivery and retention of neurotransmitter receptors, but the mechanisms underlying these processes are poorly understood. We found that differential sorting of glutamate receptor subtypes began in the endoplasmic reticulum of rat hippocampal neurons. As AMPA receptors (AMPARs) were trafficked to the plasma membrane via the conventional somatic Golgi network, NMDA receptors (NMDARs) were diverted from the somatic endoplasmic reticulum into a specialized endoplasmic reticulum subcompartment that bypasses somatic Golgi, merging instead with dendritic Golgi outposts. This endoplasmic reticulum subcompartment was composed of highly mobile vesicles containing the NMDAR subunits NR1 and NR2B, the microtubule-dependent motor protein KIF17, and the postsynaptic adaptor proteins CASK and SAP97. Our data demonstrate that the retention and trafficking of NMDARs in this endoplasmic reticulum subcompartment requires both CASK and SAP97. These findings indicate that NMDARs are sorted away from AMPARs via a non-conventional secretory pathway that utilizes dendritic Golgi outposts.
- Department of Psychiatry and Behavioral Science, Stanford University, Palo Alto, California, USA.
- Center for Neural Science and Department of Biology, New York University, New York, New York, USA.
- Department of Physiology, University of Auckland, Auckland, New Zealand.
- Department of Neurobiology, University of Chicago, Chicago, Illinois, USA.
- Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, Rhode Island, USA.
- These authors contributed equally to this work.
Correspondence to: Craig C Garner1,6 e-mail: cgarner@stanford.edu
Correspondence to: William N Green4,6 e-mail: wgreen@midway.uchicago.edu
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