LRRTM2 Interacts with Neurexin1 and Regulates Excitatory Synapse Formation

被引：300

作者：

de Wit, Joris ^{[1
]}

Sylwestrak, Emily ^{[1
]}

O'Sullivan, Matthew L. ^{[1
]}

Otto, Stefanie ^{[1
]}

Tiglio, Katie ^{[1
]}

Savas, Jeffrey N. ^{[3
]}

Yates, John R., III ^{[3
]}

Comoletti, Davide ^{[2
]}

Taylor, Palmer ^{[2
]}

Ghosh, Anirvan ^{[1
]}

机构：

[1] Univ Calif San Diego, Neurobiol Sect, Div Biol, La Jolla, CA 92093 USA

[2] Univ Calif San Diego, Dept Pharmacol, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA

[3] Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA

来源：

NEURON | 2009年 / 64卷 / 06期

关键词：

ADHESION MOLECULES; AMPA RECEPTORS; PROTEINS; PSD-95; FAMILY; DISEASE; GENE; IDENTIFICATION;

D O I：

10.1016/j.neuron.2009.12.019

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

We identify the leucine-rich repeat transmembrane protein LRRTM2 as a key regulator of excitatory synapse development and function. LRRTM2 localizes to excitatory synapses in transfected hippocampal neurons, and shRNA-mediated knockdown of LRRTM2 leads to a decrease in excitatory synapses without affecting inhibitory synapses. LRRTM2 interacts with PSD-95 and regulates surface expression of AMPA receptors, and lentivirus-mediated knockdown of LRRTM2 in vivo decreases the strength of evoked excitatory synaptic currents. Structure-function studies indicate that LRRTM2 induces presynaptic differentiation via the extracellular LRR domain. We identify Neurexin1 as a receptor for LRRTM2 based on affinity chromatography. LRRTM2 binds to both Neurexin 1 alpha and Neurexin 1 beta, and shRNA-mediated knockdown of Neurexin1 abrogates LRRTM2-induced presynaptic differentiation. These observations indicate that an LRRTM2-Neurexin1 interaction plays a critical role in regulating excitatory synapse development.

引用

页码：799 / 806

页数：8

共 28 条

[21] LRRTM3 promotes processing of amyloid-precursor protein by BACE1 and is a positional candidate gene for late-onset Alzheimer's disease [J].

Majercak, John ;

Ray, William J. ;

Espeseth, Amy ;

Simon, Adam ;

Shi, Xiao-Ping ;

Wolffe, Carrie ;

Getty, Krista ;

Marine, Shane ;

Stec, Erica ;

Ferrer, Marc ;

Strulovici, Berta ;

Bartz, Steven ;

Gates, Adam ;

Xu, Min ;

Huang, Qian ;

Ma, Lei ;

Shughrue, Paul ;

Burchard, Julja ;

Colussi, Dennis ;

Pietrak, Beth ;

Kahana, Jason ;

Beher, Dirk ;

Rosahl, Thomas ;

Shearman, Mark ;

Hazuda, Daria ;

Sachs, Alan B. ;

Koblan, Kenneth S. ;

Seabrook, Guy R. ;

Stone, David J. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (47) :17967-17972

[22] Neuroligin expressed in nonneuronal cells triggers presynaptic development in contacting axons [J].

Scheiffele, P ;

Fan, JH ;

Choih, J ;

Fetter, R ;

Serafini, T .

CELL, 2000, 101 (06) :657-669

[23] Direct interactions between PSD-95 and stargazin control synaptic AMPA receptor number [J].

Schnell, E ;

Sizemore, M ;

Karimzadegan, S ;

Chen, L ;

Bredt, DS ;

Nicoll, RA .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (21) :13902-13907

[24] The postsynaptic architecture of excitatory synapses: A more quantitative view [J].

Sheng, Morgan ;

Hoogenraad, Casper C. .

ANNUAL REVIEW OF BIOCHEMISTRY, 2007, 76 :823-847

[25] Neuroligin 1 is a postsynaptic cell-adhesion molecule of excitatory synapses [J].

Song, JY ;

Ichtchenko, K ;

Südhof, TC ;

Brose, N .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (03) :1100-1105

[26] Neuroligins and neurexins link synaptic function to cognitive disease [J].

Sudhof, Thomas C. .

NATURE, 2008, 455 (7215) :903-911

[27] Large-scale analysis of the yeast proteome by multidimensional protein identification technology [J].

Washburn, MP ;

Wolters, D ;

Yates, JR .

NATURE BIOTECHNOLOGY, 2001, 19 (03) :242-247

[28] Molecular constituents of the postsynaptic density fraction revealed by proteomic analysis using multidimensional liquid chromatography-tandem mass spectrometry [J].

Yoshimura, Y ;

Yamauchi, Y ;

Shinkawa, T ;

Taoka, M ;

Donai, H ;

Takahashi, N ;

Isobe, T ;

Yamauchi, T .

JOURNAL OF NEUROCHEMISTRY, 2004, 88 (03) :759-768

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