[No authors listed]
Leukocyte common antigen-related receptor tyrosine phosphatases (LAR-RPTPs) are evolutionarily conserved presynaptic organizers. The synaptic role of vertebrate LAR-RPTPs in vivo, however, remains unclear. In the current study, we analyzed the synaptic role of PTPÏ using newly generated, single conditional knockout (cKO) mice targeting PTPÏ. We found that the number of synapses was reduced in PTPÏ cKO cultured neurons in association with impaired excitatory synaptic transmission, abnormal vesicle localization, and abnormal synaptic ultrastructure. Strikingly, loss of presynaptic PTPÏ reduced neurotransmitter release prominently at excitatory synapses, concomitant with drastic reductions in excitatory innervations onto postsynaptic target areas in vivo. Furthermore, loss of presynaptic PTPÏ in hippocampal CA1 pyramidal neurons had no impact on postsynaptic glutamate receptor responses in subicular pyramidal neurons. Postsynaptic PTPÏ deletion had no effect on excitatory synaptic strength. Taken together, these results demonstrate that PTPÏ is a bona fide presynaptic adhesion molecule that controls neurotransmitter release and excitatory inputs.
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