title: Stress-evoked tyrosine phosphorylation of signal regulatory protein α regulates behavioral immobility in the forced swim test.
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 alpha (SIRPalpha) 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 SIRPalpha 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 SIRPalpha in the brain of wild-type mice through activation of Src family kinases. The SIRPalpha ligand CD47 was important for such SIRPalpha 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 Kvbeta2 was regulated by SIRPalpha. Thus, tyrosine phosphorylation of SIRPalpha is important for regulation of depression-like behavior in the response of the brain to stress.
authors.affiliation: Laboratory of Biosignal Sciences, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma 371-8512, Japan. ohnishih@showa.gunma-u.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohnishi
authors.forename: Takaaki
authors.initials: T
authors.lastname: Murata
authors.forename: Shinya
authors.initials: S
authors.lastname: Kusakari
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Keizo
authors.initials: K
authors.lastname: Takao
authors.forename: Toshi
authors.initials: T
authors.lastname: Maruyama
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ago
authors.forename: Ken
authors.initials: K
authors.lastname: Koda
authors.forename: Feng-Jie
authors.initials: FJ
authors.lastname: Jin
authors.forename: Katsuya
authors.initials: K
authors.lastname: Okawa
authors.forename: Per-Arne
authors.initials: PA
authors.lastname: Oldenborg
authors.forename: Hideki
authors.initials: H
authors.lastname: Okazawa
authors.forename: Yoji
authors.initials: Y
authors.lastname: Murata
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Furuya
authors.forename: Toshio
authors.initials: T
authors.lastname: Matsuda
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Miyakawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Matozaki
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D015153:Blotting, Western; D002460:Cell Line; D002540:Cerebral Cortex / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D046353:Immobility Response, Tonic / Q000502:physiology*; D051379:Mice; D017551:Microdialysis; D010766:Phosphorylation; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological / Q000502:physiology*; D013315:Stress, Psychological / Q000378:metabolism / Q000503:physiopathology*; D013550:Swimming
chemical_list: C501922:Sirpa protein, mouse; D011971:Receptors, Immunologic