PTPσ Controls Presynaptic Organization of Neurotransmitter Release Machinery at Excitatory Synapses

IScience
Kyung Ah HanJaewon Ko

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. 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 areas in 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 a bona fide presynaptic adhesion molecule that controls neurotransmitter release and excitatory inputs.

Citations

Sep 29, 2020·Frontiers in Cellular Neuroscience·Alfred Kihoon LeeHideto Takahashi
Dec 11, 2020·The FEBS Journal·Shuya Fukai, Tomoyuki Yoshida
Mar 4, 2021·ELife·Javier Emperador-MeleroPascal S Kaeser
Aug 10, 2021·Frontiers in Synaptic Neuroscience·Angelina LesnikovaEero Castrén
Oct 1, 2021·Communications Biology·Eunkyung LieEunjoon Kim

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Methods Mentioned

BETA
transfections
transmission electron microscopy
electron microscopy

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