LRRTM2 Interacts with Neurexin1 and Regulates Excitatory Synapse Formation

被引：297

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

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