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 language | English |
|---|---|
| Pages (from-to) | 10472-10483 |
| Number of pages | 12 |
| Journal | Journal of Neuroscience |
| Volume | 30 |
| Issue number | 31 |
| DOIs | |
| Publication status | Published - 04-08-2010 |
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All Science Journal Classification (ASJC) codes
- Neuroscience(all)
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Stress-evoked tyrosine phosphorylation of signal regulatory protein α regulates behavioral immobility in the forced swim test. / Ohnishi, Hiroshi; Murata, Takaaki; Kusakari, Shinya; Hayashi, Yuriko; Takao, Keizo; Maruyama, Toshi; Ago, Yukio; Koda, Ken; Jin, Feng Jie; Okawa, Katsuya; Oldenborg, Per Arne; Okazawa, Hideki; Murata, Yoji; Furuya, Nobuhiko; Matsuda, Toshio; Miyakawa, Tsuyoshi; Matozaki, Takashi.
In: Journal of Neuroscience, Vol. 30, No. 31, 04.08.2010, p. 10472-10483.Research output: Contribution to journal › Article
TY - JOUR
T1 - Stress-evoked tyrosine phosphorylation of signal regulatory protein α regulates behavioral immobility in the forced swim test
AU - Ohnishi, Hiroshi
AU - Murata, Takaaki
AU - Kusakari, Shinya
AU - Hayashi, Yuriko
AU - Takao, Keizo
AU - Maruyama, Toshi
AU - Ago, Yukio
AU - Koda, Ken
AU - Jin, Feng Jie
AU - Okawa, Katsuya
AU - Oldenborg, Per Arne
AU - Okazawa, Hideki
AU - Murata, Yoji
AU - Furuya, Nobuhiko
AU - Matsuda, Toshio
AU - Miyakawa, Tsuyoshi
AU - Matozaki, Takashi
PY - 2010/8/4
Y1 - 2010/8/4
N2 - 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.
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.
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U2 - 10.1523/JNEUROSCI.0257-10.2010
DO - 10.1523/JNEUROSCI.0257-10.2010
M3 - Article
VL - 30
SP - 10472
EP - 10483
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 31
ER -