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Neuron. 2009 Dec 24;64(6):799-806. doi: 10.1016/j.neuron.2009.12.019.

LRRTM2 interacts with Neurexin1 and regulates excitatory synapse formation.

Author information

1
Neurobiology Section, Division of Biology, University of California, San Diego, La Jolla, CA 92093, USA.

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.

PMID:
20064388
PMCID:
PMC2829666
DOI:
10.1016/j.neuron.2009.12.019
[Indexed for MEDLINE]
Free PMC Article

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