Title: Unbiased Discovery of Glypican as a Receptor for LRRTM4 in Regulating Excitatory Synapse Development
Authors: de Wit, Joris ×
O'Sullivan, Matthew L
Savas, Jeffrey N
Condomitti, Giuseppe
Caccese, Max C
Vennekens, Kristel
Yates, John R
Ghosh, Anirvan #
Issue Date: Aug-2013
Publisher: Cell Press
Series Title: Neuron vol:79 issue:4 pages:696-711
Article number: 10.1016/j.neuron.2013.06.049
Abstract: 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.
ISSN: 0896-6273
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
Laboratory of Synapse Biology (+)
× corresponding author
# (joint) last author

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