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PMID: 19620977 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

SAP97 and CASK mediate sorting of NMDA receptors through a previously unknown secretory pathway.

Nature neuroscience ·Vol. 12 ·No. 8 ·2009-08-00 ·Pages 1011-9

Jeyifous O, Waites CL, Specht CG, Fujisawa S, Schubert M, Lin EI, Marshall J, Aoki C, de Silva T, Montgomery JM, Garner CC, Green WN

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.

MeSH Terms
Adaptor Proteins, Signal Transducing/metabolism Animals Bodily Secretions/physiology Cell Compartmentation/physiology Cell Line Cells, Cultured Dendrites/metabolism,ultrastructure Endoplasmic Reticulum/metabolism,ultrastructure Golgi Apparatus/metabolism,ultrastructure Guanylate Kinases/metabolism Hippocampus/metabolism,ultrastructure Humans Kinesins/metabolism Membrane Proteins/metabolism Neurons/metabolism,ultrastructure Protein Transport/physiology Rats Rats, Sprague-Dawley Receptors, AMPA/metabolism Receptors, N-Methyl-D-Aspartate/metabolism Signal Transduction/physiology
Chemicals
Adaptor Proteins, Signal Transducing Dlg1 protein, rat KIF17 protein, mouse Membrane Proteins NR1 NMDA receptor NR2B NMDA receptor Receptors, AMPA Receptors, N-Methyl-D-Aspartate CASK kinases Guanylate Kinases Kinesins
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Jeyifous Okunola
Department of Psychiatry and Behavioral Science, Stanford University, Palo Alto, California, USA.
Waites Clarissa L
Specht Christian G
Fujisawa Sho
Schubert Manja
Lin Eric I
Marshall John
Aoki Chiye
de Silva Tharani
Montgomery Johanna M
Garner Craig C
Green William N
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Article Info
Journal
Nature neuroscience
Abbr.
Nat Neurosci
ISSN
1546-1726
DOI
10.1038/nn.2362
Published
2009-08-00
Epub
2009-00-20
Pages
1011-9
Language
English
Region
United States
NLM ID
9809671
PMCID
PMC2779056
Subset
IM
Grants
NIDA NIH HHS · P01 DA019695-01A2 · United States
NINDS NIH HHS · R56 NS043782-06 · United States
NIDA NIH HHS · DA016758 · United States
NINDS NIH HHS · R56 NS043782 · United States
NIDA NIH HHS · R01 DA016758 · United States
NEI NIH HHS · R01 EY013145-04 · United States
NINDS NIH HHS · R01 NS043782-05 · United States
NIDA NIH HHS · DA019695 · United States
NINDS NIH HHS · NS043782 · United States
NIDA NIH HHS · P01 DA019695 · United States
NINDS NIH HHS · R01 NS041091 · United States
NEI NIH HHS · P30 EY013079 · United States
NIDA NIH HHS · DA13602 · United States
NINDS NIH HHS · R01 NS043782 · United States
NEI NIH HHS · R01 EY013145 · United States
NIDA NIH HHS · R01 DA013602 · United States
NINDS NIH HHS · R25 NS080686 · United States
NEI NIH HHS · P30 EY013079-109003 · United States
NINDS NIH HHS · R01 NS041091-04 · United States
External Links
PubMed source DOI: 10.1038/nn.2362 PMC Full Text View journal details
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