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

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)1011-1019
Number of pages9
JournalNature Neuroscience
Volume12
Issue number8
DOIs
StatePublished - Aug 2009

Fingerprint

Secretory Pathway
N-Methyl-D-Aspartate Receptors
Endoplasmic Reticulum
AMPA Receptors
Neurotransmitter Receptor
Neuronal Plasticity
Glutamate Receptors
Microtubules
Proteins
Cell Membrane
Neurons

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Jeyifous, O., Waites, C. L., Specht, C. G., Fujisawa, S., Schubert, M., Lin, E. I., ... Green, W. N. (2009). SAP97 and CASK mediate sorting of NMDA receptors through a previously unknown secretory pathway. Nature Neuroscience, 12(8), 1011-1019. https://doi.org/10.1038/nn.2362

SAP97 and CASK mediate sorting of NMDA receptors through a previously unknown secretory pathway. / Jeyifous, Okunola; 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.

In: Nature Neuroscience, Vol. 12, No. 8, 08.2009, p. 1011-1019.

Research output: Contribution to journalArticle

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 2009, 'SAP97 and CASK mediate sorting of NMDA receptors through a previously unknown secretory pathway', Nature Neuroscience, vol. 12, no. 8, pp. 1011-1019. https://doi.org/10.1038/nn.2362
Jeyifous O, Waites CL, Specht CG, Fujisawa S, Schubert M, Lin EI et al. SAP97 and CASK mediate sorting of NMDA receptors through a previously unknown secretory pathway. Nature Neuroscience. 2009 Aug;12(8):1011-1019. https://doi.org/10.1038/nn.2362
Jeyifous, Okunola ; 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. / SAP97 and CASK mediate sorting of NMDA receptors through a previously unknown secretory pathway. In: Nature Neuroscience. 2009 ; Vol. 12, No. 8. pp. 1011-1019.
@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.}",
year = "2009",
month = "8",
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.

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

VL - 12

SP - 1011

EP - 1019

JO - Nature Neuroscience

JF - Nature Neuroscience

SN - 1097-6256

IS - 8

ER -