α-Actinin Anchors PSD-95 at Postsynaptic Sites

Lucas Matt; Karam Kim; Anne E. Hergarden; Tommaso Patriarchi; Zulfiqar A. Malik; Deborah K. Park; Dhrubajyoti Chowdhury; Olivia R. Buonarati; Peter B. Henderson; Çiğdem Gökçek Saraç; Yonghong Zhang; Durga Mohapatra; Mary C Horne; James B. Ames; Johannes W Hell

doi:10.1016/j.neuron.2018.01.036

α-Actinin Anchors PSD-95 at Postsynaptic Sites

Lucas Matt, Karam Kim, Anne E. Hergarden, Tommaso Patriarchi, Zulfiqar A. Malik, Deborah K. Park, Dhrubajyoti Chowdhury, Olivia R. Buonarati, Peter B. Henderson, Çiğdem Gökçek Saraç, Yonghong Zhang, Durga Mohapatra, Mary C Horne, James B. Ames, Johannes W Hell

Pharmacology

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

29 Scopus citations

Abstract

Despite the central role PSD-95 plays in anchoring postsynaptic AMPARs, how PSD-95 itself is tethered to postsynaptic sites is not well understood. Here we show that the F-actin binding protein α-actinin binds to the very N terminus of PSD-95. Knockdown (KD) of α-actinin phenocopies KD of PSD-95. Mutating lysine at position 10 or lysine at position 11 of PSD-95 to glutamate, or glutamate at position 53 or glutamate and aspartate at positions 213 and 217 of α-actinin, respectively, to lysine impairs, in parallel, PSD-95 binding to α-actinin and postsynaptic localization of PSD-95 and AMPARs. These experiments identify α-actinin as a critical PSD-95 anchor tethering the AMPAR-PSD-95 complex to postsynaptic sites. Matt et al. introduce α-actinin as a critical postsynaptic docking protein for PSD-95 and AMPARs. They found that disruption of the PSD-95-α-actinin interaction by point-mutating the essential residues on either protein leads to reduced synaptic localization of PSD-95 and AMPARs.

Original language	English (US)
Journal	Neuron
DOIs	https://doi.org/10.1016/j.neuron.2018.01.036
State	Accepted/In press - Jan 1 2018

Keywords

AMPA receptors
Dendritic spines
Hippocampus
PSD-95
Synapse
α-actinin

ASJC Scopus subject areas

Neuroscience(all)

Access to Document

10.1016/j.neuron.2018.01.036

Cite this

α-Actinin Anchors PSD-95 at Postsynaptic Sites. / Matt, Lucas; Kim, Karam; Hergarden, Anne E.; Patriarchi, Tommaso; Malik, Zulfiqar A.; Park, Deborah K.; Chowdhury, Dhrubajyoti; Buonarati, Olivia R.; Henderson, Peter B.; Gökçek Saraç, Çiğdem; Zhang, Yonghong; Mohapatra, Durga; Horne, Mary C; Ames, James B.; Hell, Johannes W.

In: Neuron, 01.01.2018.

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

@article{820172f8a258401d881310ef00e9184a,

title = "α-Actinin Anchors PSD-95 at Postsynaptic Sites",

abstract = "Despite the central role PSD-95 plays in anchoring postsynaptic AMPARs, how PSD-95 itself is tethered to postsynaptic sites is not well understood. Here we show that the F-actin binding protein α-actinin binds to the very N terminus of PSD-95. Knockdown (KD) of α-actinin phenocopies KD of PSD-95. Mutating lysine at position 10 or lysine at position 11 of PSD-95 to glutamate, or glutamate at position 53 or glutamate and aspartate at positions 213 and 217 of α-actinin, respectively, to lysine impairs, in parallel, PSD-95 binding to α-actinin and postsynaptic localization of PSD-95 and AMPARs. These experiments identify α-actinin as a critical PSD-95 anchor tethering the AMPAR-PSD-95 complex to postsynaptic sites. Matt et al. introduce α-actinin as a critical postsynaptic docking protein for PSD-95 and AMPARs. They found that disruption of the PSD-95-α-actinin interaction by point-mutating the essential residues on either protein leads to reduced synaptic localization of PSD-95 and AMPARs.",

keywords = "AMPA receptors, Dendritic spines, Hippocampus, PSD-95, Synapse, α-actinin",

author = "Lucas Matt and Karam Kim and Hergarden, {Anne E.} and Tommaso Patriarchi and Malik, {Zulfiqar A.} and Park, {Deborah K.} and Dhrubajyoti Chowdhury and Buonarati, {Olivia R.} and Henderson, {Peter B.} and {G{\"o}k{\c c}ek Sara{\c c}}, {\c C}iğdem and Yonghong Zhang and Durga Mohapatra and Horne, {Mary C} and Ames, {James B.} and Hell, {Johannes W}",

year = "2018",

month = jan,

day = "1",

doi = "10.1016/j.neuron.2018.01.036",

language = "English (US)",

journal = "Neuron",

issn = "0896-6273",

publisher = "Cell Press",

}

TY - JOUR

T1 - α-Actinin Anchors PSD-95 at Postsynaptic Sites

AU - Matt, Lucas

AU - Kim, Karam

AU - Hergarden, Anne E.

AU - Patriarchi, Tommaso

AU - Malik, Zulfiqar A.

AU - Park, Deborah K.

AU - Chowdhury, Dhrubajyoti

AU - Buonarati, Olivia R.

AU - Henderson, Peter B.

AU - Gökçek Saraç, Çiğdem

AU - Zhang, Yonghong

AU - Mohapatra, Durga

AU - Horne, Mary C

AU - Ames, James B.

AU - Hell, Johannes W

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Despite the central role PSD-95 plays in anchoring postsynaptic AMPARs, how PSD-95 itself is tethered to postsynaptic sites is not well understood. Here we show that the F-actin binding protein α-actinin binds to the very N terminus of PSD-95. Knockdown (KD) of α-actinin phenocopies KD of PSD-95. Mutating lysine at position 10 or lysine at position 11 of PSD-95 to glutamate, or glutamate at position 53 or glutamate and aspartate at positions 213 and 217 of α-actinin, respectively, to lysine impairs, in parallel, PSD-95 binding to α-actinin and postsynaptic localization of PSD-95 and AMPARs. These experiments identify α-actinin as a critical PSD-95 anchor tethering the AMPAR-PSD-95 complex to postsynaptic sites. Matt et al. introduce α-actinin as a critical postsynaptic docking protein for PSD-95 and AMPARs. They found that disruption of the PSD-95-α-actinin interaction by point-mutating the essential residues on either protein leads to reduced synaptic localization of PSD-95 and AMPARs.

AB - Despite the central role PSD-95 plays in anchoring postsynaptic AMPARs, how PSD-95 itself is tethered to postsynaptic sites is not well understood. Here we show that the F-actin binding protein α-actinin binds to the very N terminus of PSD-95. Knockdown (KD) of α-actinin phenocopies KD of PSD-95. Mutating lysine at position 10 or lysine at position 11 of PSD-95 to glutamate, or glutamate at position 53 or glutamate and aspartate at positions 213 and 217 of α-actinin, respectively, to lysine impairs, in parallel, PSD-95 binding to α-actinin and postsynaptic localization of PSD-95 and AMPARs. These experiments identify α-actinin as a critical PSD-95 anchor tethering the AMPAR-PSD-95 complex to postsynaptic sites. Matt et al. introduce α-actinin as a critical postsynaptic docking protein for PSD-95 and AMPARs. They found that disruption of the PSD-95-α-actinin interaction by point-mutating the essential residues on either protein leads to reduced synaptic localization of PSD-95 and AMPARs.

KW - AMPA receptors

KW - Dendritic spines

KW - Hippocampus

KW - PSD-95

KW - Synapse

KW - α-actinin

UR - http://www.scopus.com/inward/record.url?scp=85041670821&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85041670821&partnerID=8YFLogxK

U2 - 10.1016/j.neuron.2018.01.036

DO - 10.1016/j.neuron.2018.01.036

M3 - Article

C2 - 29429936

AN - SCOPUS:85041670821

JO - Neuron

JF - Neuron

SN - 0896-6273

ER -

α-Actinin Anchors PSD-95 at Postsynaptic Sites

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this