PTPσ Controls Presynaptic Organization of Neurotransmitter Release Machinery at Excitatory Synapses

Kyung Ah Han; Hee-Yoon Lee; Dongseok Lim; Jungsu Shin; Taek Han Yoon; Chooungku Lee; Jeong-Seop Rhee; Xinran Liu; Ji Won Um; Se-Young Choi; Jaewon Ko

doi:10.1016/j.isci.2020.101203

PTPσ Controls Presynaptic Organization of Neurotransmitter Release Machinery at Excitatory Synapses

iScience. 2020 Jun 26;23(6):101203. doi: 10.1016/j.isci.2020.101203. Epub 2020 May 28.

Authors

Kyung Ah Han¹, Hee-Yoon Lee², Dongseok Lim³, Jungsu Shin³, Taek Han Yoon³, Chooungku Lee⁴, Jeong-Seop Rhee⁴, Xinran Liu⁵, Ji Won Um¹, Se-Young Choi⁶, Jaewon Ko⁷

Affiliations

¹ Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST), 333 Techno Jungangdae-Ro, Hyeonpoong-Eup, Dalseong-Gun, Daegu 42988, Korea; Core Protein Resources Center, DGIST, 333 Techno Jungangdae-Ro, Hyeonpoong-Eup, Dalseong-Gun, Daegu 42988, Korea.
² Department of Physiology and Neuroscience, Dental Research Institute, Seoul National University School of Dentistry, Seoul 03080, Korea.
³ Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST), 333 Techno Jungangdae-Ro, Hyeonpoong-Eup, Dalseong-Gun, Daegu 42988, Korea.
⁴ Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, Göttingen 37075, Germany.
⁵ Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06510, USA.
⁶ Department of Physiology and Neuroscience, Dental Research Institute, Seoul National University School of Dentistry, Seoul 03080, Korea. Electronic address: sychoi@snu.ac.kr.
⁷ Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST), 333 Techno Jungangdae-Ro, Hyeonpoong-Eup, Dalseong-Gun, Daegu 42988, Korea. Electronic address: jaewonko@dgist.ac.kr.

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.

Keywords: Biological Sciences; Cellular Neuroscience; Molecular Neuroscience.