摘要：SummaryLeukocyte common antigen-related receptor tyrosine phosphatases (LAR-RPTPs) are evolutionarily conserved presynaptic organizers. The synaptic role of vertebrate LAR-RPTPsin vivo, however, remains unclear. In the current study, we analyzed the synaptic role of PTPσ using newly generated, single conditional knockout (cKO) mice targeting PTPσ. We found that the number of synapses was reduced in PTPσ cKO cultured neurons in association with impaired excitatory synaptic transmission, abnormal vesicle localization, and abnormal synaptic ultrastructure. Strikingly, loss of presynaptic PTPσ reduced neurotransmitter release prominently at excitatory synapses, concomitant with drastic reductions in excitatory innervations onto postsynaptic target areasin vivo. Furthermore, loss of presynaptic PTPσ in hippocampal CA1 pyramidal neurons had no impact on postsynaptic glutamate receptor responses in subicular pyramidal neurons. Postsynaptic PTPσ deletion had no effect on excitatory synaptic strength. Taken together, these results demonstrate that PTPσ is abona fidepresynaptic adhesion molecule that controls neurotransmitter release and excitatory inputs.Graphical AbstractDisplay OmittedHighlights•Conditional PTPσ KO produces specifically impaired presynaptic functions•Presynaptic PTPσ regulates glutamate release efficiency•Presynaptic PTPσ does not transsynaptically regulate postsynaptic receptor responsesBiological Sciences; Molecular Neuroscience; Cellular Neuroscience
