Title: LRRTM2 Interacts with Neurexin1 and Regulates Excitatory Synapse Formation
Authors: de Wit, Joris
Sylwestrak, Emily
O'Sullivan, Matthew L
Otto, Stefanie
Tiglio, Katie
Savas, Jeffrey N
Yates, John R., III
Comoletti, Davide
Taylor, Palmer
Ghosh, Anirvan # ×
Issue Date: Dec-2009
Publisher: Cell Press
Series Title: Neuron vol:64 issue:6 pages:799-806
Abstract: Summary
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 1α and Neurexin 1β, 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.
ISSN: 0896-6273
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Non-KU Leuven Association publications
× corresponding author
# (joint) last author

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