PTP? functions as a presynaptic receptor for the glypican-4/LRRTM4 complex and is essential for excitatory synaptic transmission.

Leukocyte common antigen-related receptor protein tyrosine phosphatases--comprising LAR, PTP?, and PTP?--are synaptic adhesion molecules that organize synapse development. Here, we identify glypican 4 (GPC-4) as a ligand for PTP?. GPC-4 showed strong (nanomolar) affinity and heparan sulfate (HS)-dependent interaction with the Ig domains of PTP?. PTP? 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 PTP?, 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, PTP? KD dramatically decreased both the frequency and amplitude of excitatory synaptic transmission. This effect was reversed by wild-type PTP?, but not by a HS-binding-defective PTP? mutant. Our results collectively suggest that presynaptic PTP?, together with GPC-4, acts in a HS-dependent manner to maintain excitatory synapse development and function.
Mesh Terms:
Analysis of Variance, Animals, Blotting, Western, Brain, Chromatography, Affinity, Chromatography, High Pressure Liquid, Gene Knockdown Techniques, Genetic Vectors, Glypicans, Heparitin Sulfate, Immunohistochemistry, Immunoprecipitation, In Situ Hybridization, Mass Spectrometry, Multiprotein Complexes, Oligonucleotides, Presynaptic Terminals, Proteins, Rats, Receptor-Like Protein Tyrosine Phosphatases, Class 2, Synaptic Transmission
Proc. Natl. Acad. Sci. U.S.A.
Date: Feb. 10, 2015
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