2024年9月30日 / 最終更新日 : 2024年9月30日 ad_y ニュース

2024年 新着論文 50　細胞情報学分野から論文が発表されました

The TrkC-PTPσ complex governs synapse maturation and anxiogenic avoidance via synaptic protein phosphorylation

EMBO J. 2024 Sep 27. doi: 10.1038/s44318-024-00252-9. Online ahead of print.

Authors

Husam Khaled  1   2 , Zahra Ghasemi #  3 , Mai Inagaki #  4 , Kyle Patel  3 , Yusuke Naito  1   5 , Benjamin Feller  1   6 , Nayoung Yi  1   2 , Farin B Bourojeni  7 , Alfred Kihoon Lee  1   5 , Nicolas Chofflet  1   5 , Artur Kania  5   7   8 , Hidetaka Kosako  9 , Masanori Tachikawa #  10 , Steven Connor #  11 , Hideto Takahashi #  12   13   14   15

Affiliations

  • 1 Synapse Development and Plasticity Research Unit, Institut de Recherches Cliniques de Montréal (IRCM), Montreal, QC, H2W 1R7, Canada.
  • 2 Department of Molecular Biology, Faculty of Medicine, Université de Montréal, Montreal, QC, H3T 1J4, Canada.
  • 3 Department of Biology, York University, Toronto, ON, M3J 1P3, Canada.
  • 4 Graduate School of Biomedical Sciences, Tokushima University, Tokushima, 770-8505, Japan.
  • 5 Integrated Program in Neuroscience, McGill University, Montreal, QC, H3A 2B2, Canada.
  • 6 Department of Neuroscience, Faculty of medicine, Université de Montréal, Montreal, QC, H3T 1J4, Canada.
  • 7 Neural Circuit Development Laboratory, Institut de Recherches Cliniques de Montréal (IRCM), Montreal, QC, H2W 1R7, Canada.
  • 8 Division of Experimental Medicine, McGill University, Montreal, QC, H3A 0G4, Canada.
  • 9 Division of Cell Signaling, Fujii Memorial Institute of Medical Sciences, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, 770-8503, Japan.
  • 10 Graduate School of Biomedical Sciences, Tokushima University, Tokushima, 770-8505, Japan. tachikaw@tokushima-u.ac.jp.
  • 11 Department of Biology, York University, Toronto, ON, M3J 1P3, Canada. saconnor@yorku.ca.
  • 12 Synapse Development and Plasticity Research Unit, Institut de Recherches Cliniques de Montréal (IRCM), Montreal, QC, H2W 1R7, Canada. Hideto.Takahashi@ircm.qc.ca.
  • 13 Department of Molecular Biology, Faculty of Medicine, Université de Montréal, Montreal, QC, H3T 1J4, Canada. Hideto.Takahashi@ircm.qc.ca.
  • 14 Integrated Program in Neuroscience, McGill University, Montreal, QC, H3A 2B2, Canada. Hideto.Takahashi@ircm.qc.ca.
  • 15 Division of Experimental Medicine, McGill University, Montreal, QC, H3A 0G4, Canada. Hideto.Takahashi@ircm.qc.ca.
# Contributed equally.

Abstract

The precise organization of pre- and postsynaptic terminals is crucial for normal synaptic function in the brain. In addition to its canonical role as a neurotrophin-3 receptor tyrosine kinase, postsynaptic TrkC promotes excitatory synapse organization through interaction with presynaptic receptor-type tyrosine phosphatase PTPσ. To isolate the synaptic organizer function of TrkC from its role as a neurotrophin-3 receptor, we generated mice carrying TrkC point mutations that selectively abolish PTPσ binding. The excitatory synapses in mutant mice had abnormal synaptic vesicle clustering and postsynaptic density elongation, more silent synapses, and fewer active synapses, which additionally exhibited enhanced basal transmission with impaired release probability. Alongside these phenotypes, we observed aberrant synaptic protein phosphorylation, but no differences in the neurotrophin signaling pathway. Consistent with reports linking these aberrantly phosphorylated proteins to neuropsychiatric disorders, mutant TrkC knock-in mice displayed impaired social responses and increased avoidance behavior. Thus, through its regulation of synaptic protein phosphorylation, the TrkC-PTPσ complex is crucial for the maturation, but not formation, of excitatory synapses in vivo.

Keywords: Avoidance Behavior; Neurotrophin Receptor; Protein Phosphorylation; Social Novelty; Synapse Organizer.

 

カテゴリー
ニュース