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

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.

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Neurovetenskaper hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Neurosciences hsv//eng
norepinephrine reuptake inhibitor; assessing antidepressant activity; integrin-associated protein; synaptic plasticity; adhesion molecules; knockout mice; axon guidance; receptor; hippocampus; depression

Murata, TakaakiGunma University, Gunma University Graduate School of Medicine (author)
Kusakari, ShinyaGunma University (author)
Hayashi, YurikoGunma University (author)
Takao, KeizoKyoto University Graduate School of Medicine, Fujita Health University (author)
Maruyama, ToshiGunma University (author)
Ago, YukioOsaka University (author)
Koda, Ken (author)
Jin, Feng-JieGunma University (author)
Okawa, KatsuyaKyowa Hakko Kirin Company Ltd., Takasaki (author)
Oldenborg, Per-ArneUmeå universitet,Histologi med cellbiologi(Swepub:umu)peol0001 (author)
Okazawa, HidekiGunma University (author)
Murata, YojiGunma University (author)
Furuya, NobuhikoGunma University Graduate School of Medicine (author)
Matsuda, Toshio (author)
Miyakawa, TsuyoshiKyoto University Graduate School of Medicine, Fujita Health University (author)
Matozaki, TakashiGunma University, Kobe University Graduate School of Medicine (author)
Gunma UniversityGunma University, Gunma University Graduate School of Medicine (creator_code:org_t)

By the author/editor: Ohnishi, Hiroshi; Murata, Takaaki; Kusakari, Shinya; Hayashi, Yuriko; Takao, Keizo; Maruyama, Toshi; show more...; Ago, Yukio; Koda, Ken; Jin, Feng-Jie; Okawa, Katsuya; Oldenborg, Per-A ...; Okazawa, Hideki; Murata, Yoji; Furuya, Nobuhiko; Matsuda, Toshio; Miyakawa, Tsuyos ...; Matozaki, Takash ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Neurosciences

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