Premium
Receptor protein tyrosine phosphatase sigma regulates synapse structure, function and plasticity
Author(s) -
Horn Katherine E.,
Xu Bin,
Gobert Delphine,
Hamam Bassam N.,
Thompson Katherine M.,
Wu ChiaLun,
Bouchard JeanFrançois,
Uetani Noriko,
Racine Ronald J.,
Tremblay Michel L.,
Ruthazer Edward S.,
Chapman C. Andrew,
Kennedy Timothy E.
Publication year - 2012
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2012.07762.x
Subject(s) - synapse , protein tyrosine phosphatase , biology , synaptic plasticity , microbiology and biotechnology , excitatory synapse , neuroscience , postsynaptic potential , synaptogenesis , long term potentiation , phosphatase , neurotransmission , receptor , biochemistry , signal transduction , phosphorylation
J. Neurochem. (2012) 122 , 147–161. Abstract The mechanisms that regulate synapse formation and maintenance are incompletely understood. In particular, relatively few inhibitors of synapse formation have been identified. Receptor protein tyrosine phosphatase σ (RPTPσ), a transmembrane tyrosine phosphatase, is widely expressed by neurons in developing and mature mammalian brain, and functions as a receptor for chondroitin sulfate proteoglycans that inhibits axon regeneration following injury. In this study, we address RPTPσ function in the mature brain. We demonstrate increased axon collateral branching in the hippocampus of RPTPσ null mice during normal aging or following chemically induced seizure, indicating that RPTPσ maintains neural circuitry by inhibiting axonal branching. Previous studies demonstrated a role for pre‐synaptic RPTPσ promoting synaptic differentiation during development; however, subcellular fractionation revealed enrichment of RPTPσ in post‐synaptic densities. We report that neurons lacking RPTPσ have an increased density of pre‐synaptic varicosities in vitro and increased dendritic spine density and length in vivo . RPTPσ knockouts exhibit an increased frequency of miniature excitatory post‐synaptic currents, and greater paired‐pulse facilitation, consistent with increased synapse density but reduced synaptic efficiency. Furthermore, RPTPσ nulls exhibit reduced long‐term potentiation and enhanced novel object recognition memory. We conclude that RPTPσ limits synapse number and regulates synapse structure and function in the mature CNS.