First Author | Han KA | Year | 2020 |
Journal | iScience | Volume | 23 |
Issue | 6 | Pages | 101203 |
PubMed ID | 32516721 | Mgi Jnum | J:301632 |
Mgi Id | MGI:6506876 | Doi | 10.1016/j.isci.2020.101203 |
Citation | Han KA, et al. (2020) PTPsigma Controls Presynaptic Organization of Neurotransmitter Release Machinery at Excitatory Synapses. iScience 23(6):101203 |
abstractText | 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 PTPsigma using newly generated, single conditional knockout (cKO) mice targeting PTPsigma. We found that the number of synapses was reduced in PTPsigma cKO cultured neurons in association with impaired excitatory synaptic transmission, abnormal vesicle localization, and abnormal synaptic ultrastructure. Strikingly, loss of presynaptic PTPsigma reduced neurotransmitter release prominently at excitatory synapses, concomitant with drastic reductions in excitatory innervations onto postsynaptic target areas in vivo. Furthermore, loss of presynaptic PTPsigma in hippocampal CA1 pyramidal neurons had no impact on postsynaptic glutamate receptor responses in subicular pyramidal neurons. Postsynaptic PTPsigma deletion had no effect on excitatory synaptic strength. Taken together, these results demonstrate that PTPsigma is a bona fide presynaptic adhesion molecule that controls neurotransmitter release and excitatory inputs. |