Circuit-specific regulation of synapse formation by the protein tyrosine phosphatase PTP$\sigma$

Abstract

Cell Adhesion Molecule) initiates synapse formation via interacting with specific binding partners. However, functions of CAM during maintenance period and plasticity are shortly investigated. Here, I discovered an important presynaptic hub CAM, PTP$\sigma$, stabilizes NMDA-R in hippocampal SC-CA1 synapses by trans-synaptic manner, without affecting synapse formation. Surprisingly, this NMDA-R regulation works through intracellular domains and phosphatase activity of PTP$\sigma$, rather than famous extracellular bindings known to mediating synapse formation. Lacking PTP$\sigma$ causes broad range of phosphor-tyrosine level changes across the synaptic cleft, and one/many of those substrates is highly probable to mediate NMDA-R function regulation. In behavioral-wide, aberrant NMDA-R function in SC-CA1 by presynaptic KO of PTP$\sigma$, as well as postsynaptic KD of essential subunit of NMDA-R, causes impairment of novelty recognition.

CAM (