| Literature DB >> 20064388 |
Joris de Wit1, Emily Sylwestrak, Matthew L O'Sullivan, Stefanie Otto, Katie Tiglio, Jeffrey N Savas, John R Yates, Davide Comoletti, Palmer Taylor, Anirvan Ghosh.
Abstract
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 1alpha and Neurexin 1beta, 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. 2009 Elsevier Inc. All rights reserved.Entities:
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Year: 2009 PMID： 20064388 PMCID： PMC2829666 DOI： 10.1016/j.neuron.2009.12.019
Source DB: PubMed Journal: Neuron ISSN： 0896-6273 Impact factor: 17.173