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 | |
| State | Accepted/In press - Jan 1 2018 |
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Keywords
- AMPA receptors
- Dendritic spines
- Hippocampus
- PSD-95
- Synapse
- α-actinin
ASJC Scopus subject areas
- Neuroscience(all)
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
}
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 -