Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102104/1/emboj7601065.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102104/2/emboj7601065-sup-0001.pd

Adesnik H

Barry MF

Beique JC

Boyd C

Bredt DS

Brown TC

Chamila N Rupasinghe

Colledge M

Donald S Backos

Ehrlich I

El-Husseini AE

El-Husseini Ael D

Esteban JA

Finger FP

Garner CC

Gerges NZ

Groc L

Hayashi Y

Hazuka CD

Henley JM

Horton AC

Hsu SC

Inoue M

José A Esteban

Kee Y

Kim E

Kopec CD

Kornau HC

Luscher C

Malinow R

Mark R Spaller

McGee AW

Naisbitt S

Nashaat Z Gerges

Niethammer M

Nishimune A

Nong Y

Park M

Passafaro M

Peng J

Perez-Otano I

Piccini A

Prybylowski K

Riefler GM

Sans N

Scannevin RH

Sheng M

Shi S

Shin DM

Song I

Steiner P

Tardin C

TerBush DR

Ting AE

Triller A

Vega IE

Vik-Mo EO

Walikonis RS

Wang S

Wyszynski M

Yamagata M

Yeaman C

The EMBO Journal

English

PubMed

Gerges, Nashaat Z

Backos, Donald S

Rupasinghe, Chamila N

Spaller, Mark R

Esteban, José A

Deep Blue Documents

Dual role of the exocyst in AMPA receptor targeting and insertion into the postsynaptic membrane

Intracellular membrane trafficking of glutamate receptors at excitatory synapses is critical for synaptic function. However, little is known about the specialized trafficking events occurring at the postsynaptic membrane. We have found that two components of the exocyst complex, Sec8 and Exo70, separately control synaptic targeting and insertion of AMPA-type glutamate receptors. Sec8 controls the directional movement of receptors towards synapses through PDZ-dependent interactions. In contrast, Exo70 mediates receptor insertion at the postsynaptic membrane, but it does not participate in receptor targeting. Thus, interference with Exo70 function accumulates AMPA receptors inside the spine, forming a complex physically associated, but not yet fused with the postsynaptic membrane. Electron microscopic analysis of these complexes indicates that Exo70 mediates AMPA receptor insertion directly within the postsynaptic density, rather than at extrasynaptic membranes. Therefore, we propose a molecular and anatomical model that dissects AMPA receptor sorting and synaptic delivery within the spine, and uncovers new functions of the exocyst at the postsynaptic membrane.This work was supported by grants from the National Institute of
Mental Health (grant MH070417) and the National Alliance for Research on Schizophrenia and
Depression (NARSAD) to J.A.E, and grant GM63032 from the National Institute of General
Medical Sciences to M.R.S. We also thank Dr. Thomas Coles for sponsoring J.A.E. as an
Investigator of the National Alliance for the Mentally Ill (NAMI).Peer reviewe

Dual role of the exocyst in AMPA receptor targeting and insertion into the postsynaptic membrane

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