Leukocyte common antigen-related receptor protein tyrosine phosphatases-comprising LAR, PTPaδ, and PTPoσ-are synaptic adhesion molecules that organize synapse development. Here, we identify glypican 4 (GPC-4) as a ligand for PTPσ GPC-4 showed strong (nanomolar) affinity and heparan sulfate (HS)-dependent interaction with the Ig domains of PTPσPTPσ bound only to proteolytically cleaved GPC-4 and formed additional complex with leucine-rich repeat transmembrane protein 4 (LRRTM4) in rat brains. Moreover, single knockdown (KD) of PTPσ but not LAR, in cultured neurons significantly reduced the synaptogenic activity of LRRTM4, a postsynaptic ligand of GPC-4, in heterologous synapse-formation assays. Finally, PTPσ KD dramatically decreased both the frequency and amplitude of excitatory synaptic transmission. This effect was reversed by wild-type PTPoσ but not by a HS-binding-defective PTPσ mutant. Our results collectively suggest that presynaptic PTPσ together with GPC-4, acts in a HS-dependent manner to maintain excitatory synapse development and function. PTPσglypicanLRRTM4 synaptic cell adhesionheparan sulfate.
|Number of pages||6|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|Publication status||Published - 2015 Feb 10|
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