Stress-evoked tyrosine phosphorylation of signal regulatory protein α regulates behavioral immobility in the forced swim test
2010 (English)In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 30, no 31, 10472-10483 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2010. Vol. 30, no 31, 10472-10483 p.
norepinephrine reuptake inhibitor; assessing antidepressant activity; integrin-associated protein; synaptic plasticity; adhesion molecules; knockout mice; axon guidance; receptor; hippocampus; depression
IdentifiersURN: urn:nbn:se:umu:diva-41355DOI: 10.1523/JNEUROSCI.0257-10.2010ISI: 000280789600021PubMedID: 20685990OAI: oai:DiVA.org:umu-41355DiVA: diva2:405685