RT Journal Article
SR Electronic
T1 Stress-Evoked Tyrosine Phosphorylation of Signal Regulatory Protein α Regulates Behavioral Immobility in the Forced Swim Test
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 10472
OP 10483
DO 10.1523/JNEUROSCI.0257-10.2010
VO 30
IS 31
A1 Hiroshi Ohnishi
A1 Takaaki Murata
A1 Shinya Kusakari
A1 Yuriko Hayashi
A1 Keizo Takao
A1 Toshi Maruyama
A1 Yukio Ago
A1 Ken Koda
A1 Feng-Jie Jin
A1 Katsuya Okawa
A1 Per-Arne Oldenborg
A1 Hideki Okazawa
A1 Yoji Murata
A1 Nobuhiko Furuya
A1 Toshio Matsuda
A1 Tsuyoshi Miyakawa
A1 Takashi Matozaki
YR 2010
UL http://www.jneurosci.org/content/30/31/10472.abstract
AB 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.