Linkage of Non-receptor Tyrosine Kinase Fyn to mGlu5 Receptors in Striatal Neurons in a Depression Model.

Neuroscience
Li-Min Mao, John Q Wang

Abstract

The Src family kinase (SFK) is a subfamily of non-receptor tyrosine kinases. The SFK member Fyn is enriched at synaptic sites in the limbic reward circuit and plays a pivotal role in the regulation of glutamate receptors. In this study, we investigated changes in phosphorylation and function of the two key SFK members (Fyn and Src) and SFK interactions with a metabotropic glutamate (mGlu) receptor in the limbic striatum of adult rats in response to chronic passive stress, i.e., prolonged social isolation which is a pre-validated animal paradigm modeling depression in adulthood. In rats that showed typical anhedonic/depression-like behavior after chronic social isolation, phosphorylation of SFKs at a conserved and activation-associated autophosphorylation site (Y416) was not altered in the two subdivisions of the striatum, the nucleus accumbens and caudate putamen. The total level of phosphorylation and kinase activity of individual Fyn and Src immunopurified from the striatum also remained stable after social isolation. Noticeably, Fyn and Src were found to interact with a Gαq-coupled mGlu5 receptor in striatal neurons. The interaction of Fyn with mGlu5 receptors was selectively elevated in socially isolated rats. Moreover, soc...Continue Reading

Citations

Apr 27, 2021·Pharmacology & Therapeutics·Cong-Yuan XiaWei-Ku Zhang

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