Quaternary structure, protein dynamics, and synaptic function of SAP97 controlled by L27 domain interactions

Terunaga Nakagawa, Kensuke Futai, Hilal A. Lashuel, Irene Lo, Kenichi Okamoto, Thomas Walz, Yasunori Hayashi, Morgan Sheng

Research output: Contribution to journalArticle

192 Citations (Scopus)

Abstract

Single-particle electron microscopy (EM) combined with biochemical measurements revealed the molecular shape of SAP97 and a monomer-dimer transition that depended on the N-terminal L27 domain. Overexpression of SAP97 drove GluR1 to synapses, potentiated AMPA receptor (AMPAR) excitatory postsynaptic currents (EPSCs), and occluded LTP. Synaptic potentiation and GluR1 delivery were dissociable by L27 domain mutants that inhibit multimerization of SAP97. Loss of potentiation was correlated with faster turnover of monomeric SAP97 mutants in dendritic spines. We propose that L27-mediated interactions of SAP97 with itself or other proteins regulate the synaptic delivery of AMPARs. RNAi knockdown of endogenous PSD-95 depleted surface GluR1 and impaired AMPA EPSCs. In contrast, RNAi knockdown of endogenous SAP97 reduced surface expression of both GluR1 and GluR2 and inhibited both AMPA and NMDA EPSCs. Thus SAP97 has a broader role than its close relative, PSD-95, in the maintenance of synaptic function.

Original languageEnglish
Pages (from-to)453-467
Number of pages15
JournalNeuron
Volume44
Issue number3
DOIs
Publication statusPublished - 28 Oct 2004
Externally publishedYes

Fingerprint

Quaternary Protein Structure
Excitatory Postsynaptic Potentials
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
RNA Interference
Dendritic Spines
AMPA Receptors
N-Methylaspartate
Synapses
Electron Microscopy
Maintenance
Proteins

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Nakagawa, T., Futai, K., Lashuel, H. A., Lo, I., Okamoto, K., Walz, T., ... Sheng, M. (2004). Quaternary structure, protein dynamics, and synaptic function of SAP97 controlled by L27 domain interactions. Neuron, 44(3), 453-467. https://doi.org/10.1016/j.neuron.2004.10.012

Quaternary structure, protein dynamics, and synaptic function of SAP97 controlled by L27 domain interactions. / Nakagawa, Terunaga; Futai, Kensuke; Lashuel, Hilal A.; Lo, Irene; Okamoto, Kenichi; Walz, Thomas; Hayashi, Yasunori; Sheng, Morgan.

In: Neuron, Vol. 44, No. 3, 28.10.2004, p. 453-467.

Research output: Contribution to journalArticle

Nakagawa, T, Futai, K, Lashuel, HA, Lo, I, Okamoto, K, Walz, T, Hayashi, Y & Sheng, M 2004, 'Quaternary structure, protein dynamics, and synaptic function of SAP97 controlled by L27 domain interactions', Neuron, vol. 44, no. 3, pp. 453-467. https://doi.org/10.1016/j.neuron.2004.10.012
Nakagawa, Terunaga ; Futai, Kensuke ; Lashuel, Hilal A. ; Lo, Irene ; Okamoto, Kenichi ; Walz, Thomas ; Hayashi, Yasunori ; Sheng, Morgan. / Quaternary structure, protein dynamics, and synaptic function of SAP97 controlled by L27 domain interactions. In: Neuron. 2004 ; Vol. 44, No. 3. pp. 453-467.
@article{d63882807f9e40b8b6d263007dc56bc3,
title = "Quaternary structure, protein dynamics, and synaptic function of SAP97 controlled by L27 domain interactions",
abstract = "Single-particle electron microscopy (EM) combined with biochemical measurements revealed the molecular shape of SAP97 and a monomer-dimer transition that depended on the N-terminal L27 domain. Overexpression of SAP97 drove GluR1 to synapses, potentiated AMPA receptor (AMPAR) excitatory postsynaptic currents (EPSCs), and occluded LTP. Synaptic potentiation and GluR1 delivery were dissociable by L27 domain mutants that inhibit multimerization of SAP97. Loss of potentiation was correlated with faster turnover of monomeric SAP97 mutants in dendritic spines. We propose that L27-mediated interactions of SAP97 with itself or other proteins regulate the synaptic delivery of AMPARs. RNAi knockdown of endogenous PSD-95 depleted surface GluR1 and impaired AMPA EPSCs. In contrast, RNAi knockdown of endogenous SAP97 reduced surface expression of both GluR1 and GluR2 and inhibited both AMPA and NMDA EPSCs. Thus SAP97 has a broader role than its close relative, PSD-95, in the maintenance of synaptic function.",
author = "Terunaga Nakagawa and Kensuke Futai and Lashuel, {Hilal A.} and Irene Lo and Kenichi Okamoto and Thomas Walz and Yasunori Hayashi and Morgan Sheng",
year = "2004",
month = "10",
day = "28",
doi = "10.1016/j.neuron.2004.10.012",
language = "English",
volume = "44",
pages = "453--467",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "3",

}

TY - JOUR

T1 - Quaternary structure, protein dynamics, and synaptic function of SAP97 controlled by L27 domain interactions

AU - Nakagawa, Terunaga

AU - Futai, Kensuke

AU - Lashuel, Hilal A.

AU - Lo, Irene

AU - Okamoto, Kenichi

AU - Walz, Thomas

AU - Hayashi, Yasunori

AU - Sheng, Morgan

PY - 2004/10/28

Y1 - 2004/10/28

N2 - Single-particle electron microscopy (EM) combined with biochemical measurements revealed the molecular shape of SAP97 and a monomer-dimer transition that depended on the N-terminal L27 domain. Overexpression of SAP97 drove GluR1 to synapses, potentiated AMPA receptor (AMPAR) excitatory postsynaptic currents (EPSCs), and occluded LTP. Synaptic potentiation and GluR1 delivery were dissociable by L27 domain mutants that inhibit multimerization of SAP97. Loss of potentiation was correlated with faster turnover of monomeric SAP97 mutants in dendritic spines. We propose that L27-mediated interactions of SAP97 with itself or other proteins regulate the synaptic delivery of AMPARs. RNAi knockdown of endogenous PSD-95 depleted surface GluR1 and impaired AMPA EPSCs. In contrast, RNAi knockdown of endogenous SAP97 reduced surface expression of both GluR1 and GluR2 and inhibited both AMPA and NMDA EPSCs. Thus SAP97 has a broader role than its close relative, PSD-95, in the maintenance of synaptic function.

AB - Single-particle electron microscopy (EM) combined with biochemical measurements revealed the molecular shape of SAP97 and a monomer-dimer transition that depended on the N-terminal L27 domain. Overexpression of SAP97 drove GluR1 to synapses, potentiated AMPA receptor (AMPAR) excitatory postsynaptic currents (EPSCs), and occluded LTP. Synaptic potentiation and GluR1 delivery were dissociable by L27 domain mutants that inhibit multimerization of SAP97. Loss of potentiation was correlated with faster turnover of monomeric SAP97 mutants in dendritic spines. We propose that L27-mediated interactions of SAP97 with itself or other proteins regulate the synaptic delivery of AMPARs. RNAi knockdown of endogenous PSD-95 depleted surface GluR1 and impaired AMPA EPSCs. In contrast, RNAi knockdown of endogenous SAP97 reduced surface expression of both GluR1 and GluR2 and inhibited both AMPA and NMDA EPSCs. Thus SAP97 has a broader role than its close relative, PSD-95, in the maintenance of synaptic function.

UR - http://www.scopus.com/inward/record.url?scp=7044271080&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=7044271080&partnerID=8YFLogxK

U2 - 10.1016/j.neuron.2004.10.012

DO - 10.1016/j.neuron.2004.10.012

M3 - Article

VL - 44

SP - 453

EP - 467

JO - Neuron

JF - Neuron

SN - 0896-6273

IS - 3

ER -