Unbiased Discovery of Glypican as a Receptor for LRRTM4 in Regulating Excitatory Synapse Development

被引：116

作者：

de Wit, Joris ^{[1
,4
,5
]}

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

Savas, Jeffrey N. ^{[2
]}

Condomitti, Giuseppe ^{[4
,5
]}

Caccese, Max C. ^{[1
]}

Vennekens, Kristel M. ^{[4
,5
]}

Yates, John R., III ^{[2
]}

Ghosh, Anirvan ^{[1
,3
]}

机构：

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

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

[3] F Hoffmann La Roche, Neurosci Discovery, CH-4070 Basel, Switzerland

[4] VIB Ctr Biol Dis, B-3000 Louvain, Belgium

[5] Katholieke Univ Leuven, Ctr Human Genet, B-3000 Louvain, Belgium

来源：

NEURON | 2013年 / 79卷 / 04期

关键词：

HEPARAN-SULFATE PROTEOGLYCAN; NERVOUS-SYSTEM; ADHESION MOLECULES; DENDRITIC SPINES; EXPRESSION; AMPA; PROTEINS; FAMILY; LIGAND; AXONS;

D O I：

10.1016/j.neuron.2013.06.049

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Leucine-rich repeat (LRR) proteins have recently been identified as important regulators of synapse development and function, but for many LRR proteins the ligand-receptor interactions are not known. Here we identify the heparan sulfate (HS) proteoglycan glypican as a receptor for LRRTM4 using an unbiased proteomics-based approach. Glypican binds LRRTM4, but not LRRTM2, in an HS-dependent manner. Glypican 4 (GPC4) and LRRTM4 localize to the pre- and postsynaptic membranes of excitatory synapses, respectively. Consistent with a trans-synaptic interaction, LRRTM4 triggers GPC4 clustering in contacting axons and GPC4 induces clustering of LRRTM4 in contacting dendrites in an HS-dependent manner. LRRTM4 positively regulates excitatory synapse development in cultured neurons and in vivo, and the synaptogenic activity of LRRTM4 requires the presence of HS on the neuronal surface. Our results identify glypican as an LRRTM4 receptor and indicate that a trans-synaptic glypican-LRRTM4 interaction regulates excitatory synapse development.

引用

页码：696 / 711

页数：16

共 33 条

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