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bioRxiv · 10.1101/2020.01.10.901546

Presynaptic PTPσ organizes neurotransmitter release machinery at excitatory synapses

Han, K. A.·Lee, H.-Y.·Lim, D.·Shin, J.·Yoon, T. H.·Lee, C.·Liu, X.·Rhee, J.-S.·Um, J. W.·Choi, S. Y.·Ko, J.
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Abstract

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. This study systematically analyzed the effects of genetic deletions of LAR-RPTP genes by generating single conditional knockout (cKO) mice targeting PTP{sigma} and PTP{delta}. Although the numbers of synapses were reduced in cultured neurons deficient in individual PTPs, abnormalities in synaptic transmission, synaptic ultrastructures, and vesicle localization were observed only in PTP{sigma}-deficient neurons. Strikingly, loss of presynaptic PTP{sigma} reduced neurotransmitter release prominently at excitatory synapses, concomitant with drastic reductions in excitatory innervations onto postsynaptic target areas in vivo. However, postsynaptic PTP{sigma} deletion had no effect on excitatory synaptic strength. Furthermore, conditional deletion of PTP{sigma} in ventral CA1 specifically altered anxiety-like behaviors. Taken together, these results demonstrate that PTP{sigma} is a bona fide presynaptic adhesion molecule that controls neurotransmitter release and excitatory inputs.

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Han, K. A., Lee, H.-Y., Lim, D., Shin, J., Yoon, T. H., Lee, C., Liu, X., Rhee, J.-S., Um, J. W., Choi, S. Y., Ko, J.. 2020-01-10. Presynaptic PTPσ organizes neurotransmitter release machinery at excitatory synapses. https://doi.org/10.1101/2020.01.10.901546

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