Stress-evoked tyrosine phosphorylation of signal regulatory protein α regulates behavioral immobility in the forced swim test

Hiroshi Ohnishi, Takaaki Murata, Shinya Kusakari, Yuriko Hayashi, Keizo Takao, Toshi Maruyama, Yukio Ago, Ken Koda, Feng Jie Jin, Katsuya Okawa, Per Arne Oldenborg, Hideki Okazawa, Yoji Murata, Nobuhiko Furuya, Toshio Matsuda, Tsuyoshi Miyakawa, Takashi Matozaki

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28 Citations (Scopus)

Abstract

Severe stress induces changes in neuronal function that are implicated in stress-related disorders such as depression. The molecular mechanisms underlying the response of the brain to stress remain primarily unknown, however. Signal regulatory protein α (SIRPα) is an Ig-superfamily protein that undergoes tyrosine phosphorylation and binds the protein tyrosine phosphatase Shp2. Here we show that mice expressing a form of SIRPα that lacks most of the cytoplasmic region manifest prolonged immobility (depression-like behavior) in the forced swim (FS) test. FS stress induced marked tyrosine phosphorylation of SIRPα in the brain of wild-type mice through activation of Src family kinases. The SIRPα ligand CD47 was important for such SIRPα phosphorylation, and CD47-deficient mice also manifested prolonged immobility in the FS test. Moreover, FS stress-induced tyrosine phosphorylation of both the NR2B subunit of the NMDA subtype of glutamate receptor and the K +-channel subunit Kvβ2 was regulated by SIRPα. Thus, tyrosine phosphorylation of SIRPα is important for regulation of depression-like behavior in the response of the brain to stress.

Original languageEnglish
Pages (from-to)10472-10483
Number of pages12
JournalJournal of Neuroscience
Volume30
Issue number31
DOIs
Publication statusPublished - 04-08-2010

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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    Ohnishi, H., Murata, T., Kusakari, S., Hayashi, Y., Takao, K., Maruyama, T., Ago, Y., Koda, K., Jin, F. J., Okawa, K., Oldenborg, P. A., Okazawa, H., Murata, Y., Furuya, N., Matsuda, T., Miyakawa, T., & Matozaki, T. (2010). Stress-evoked tyrosine phosphorylation of signal regulatory protein α regulates behavioral immobility in the forced swim test. Journal of Neuroscience, 30(31), 10472-10483. https://doi.org/10.1523/JNEUROSCI.0257-10.2010