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

Okunola Jeyifous; Clarissa L. Waites; Christian G. Specht; Sho Fujisawa; Manja Schubert; Eric I. Lin; John Marshall; Chiye Aoki; Tharani De Silva; Johanna M. Montgomery; Craig C. Garner; William N. Green

doi:10.1038/nn.2362

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

Okunola Jeyifous, Clarissa L. Waites, Christian G. Specht, Sho Fujisawa, Manja Schubert, Eric I. Lin, John Marshall, Chiye Aoki, Tharani De Silva, Johanna M. Montgomery, Craig C. Garner, William N. Green

Neural Science

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Pages (from-to)	1011-1019
Number of pages	9
Journal	Nature Neuroscience
Volume	12
Issue number	8
DOIs	https://doi.org/10.1038/nn.2362
State	Published - Aug 2009

ASJC Scopus subject areas

General Neuroscience

Access to Document

10.1038/nn.2362

Cite this

@article{c28511254b7e407481ea2b2508b775f0,

title = "SAP97 and CASK mediate sorting of NMDA receptors through a previously unknown secretory pathway",

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.",

author = "Okunola Jeyifous and Waites, {Clarissa L.} and Specht, {Christian G.} and Sho Fujisawa and Manja Schubert and Lin, {Eric I.} and John Marshall and Chiye Aoki and {De Silva}, Tharani and Montgomery, {Johanna M.} and Garner, {Craig C.} and Green, {William N.}",

note = "Funding Information: We would like to thank S. Leal-Ortiz for assistance with the generation of lentivirus and shRNA, L.A. Needleman and J. Marks. Also, thanks to B. Margolis for the CASK constructs, J. Lippincott-Schwartz for the Galtase-GFP construct and V. Bindokas for help and advice with imaging protocols. This work was supported by the Nancy Pritzker Family and US National Institutes of Health grant DA016758 to C.C.G., a Deutsche Forschungsgemeinschaft postdoctoral fellowship to C.G.S., The Marsden Fund (Royal Society of New Zealand) to J.M.M., US National Institutes of Health grants NS043782, DA13602 and DA019695 to W.N.G., and the Albert & Ellen Grass Faculty Award to W.N.G. and J.M.",

year = "2009",

month = aug,

doi = "10.1038/nn.2362",

language = "English (US)",

volume = "12",

pages = "1011--1019",

journal = "Nature Neuroscience",

issn = "1097-6256",

publisher = "Nature Publishing Group",

number = "8",

}

TY - JOUR

T1 - SAP97 and CASK mediate sorting of NMDA receptors through a previously unknown secretory pathway

AU - Jeyifous, Okunola

AU - Waites, Clarissa L.

AU - Specht, Christian G.

AU - Fujisawa, Sho

AU - Schubert, Manja

AU - Lin, Eric I.

AU - Marshall, John

AU - Aoki, Chiye

AU - De Silva, Tharani

AU - Montgomery, Johanna M.

AU - Garner, Craig C.

AU - Green, William N.

N1 - Funding Information: We would like to thank S. Leal-Ortiz for assistance with the generation of lentivirus and shRNA, L.A. Needleman and J. Marks. Also, thanks to B. Margolis for the CASK constructs, J. Lippincott-Schwartz for the Galtase-GFP construct and V. Bindokas for help and advice with imaging protocols. This work was supported by the Nancy Pritzker Family and US National Institutes of Health grant DA016758 to C.C.G., a Deutsche Forschungsgemeinschaft postdoctoral fellowship to C.G.S., The Marsden Fund (Royal Society of New Zealand) to J.M.M., US National Institutes of Health grants NS043782, DA13602 and DA019695 to W.N.G., and the Albert & Ellen Grass Faculty Award to W.N.G. and J.M.

PY - 2009/8

Y1 - 2009/8

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=68149163556&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=68149163556&partnerID=8YFLogxK

U2 - 10.1038/nn.2362

DO - 10.1038/nn.2362

M3 - Article

C2 - 19620977

AN - SCOPUS:68149163556

SN - 1097-6256

VL - 12

SP - 1011

EP - 1019

JO - Nature Neuroscience

JF - Nature Neuroscience

IS - 8

ER -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this