期刊
MOLECULAR AND CELLULAR NEUROSCIENCE
卷 44, 期 2, 页码 129-134出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.mcn.2010.03.002
关键词
GABA(A) receptor; Tyrosine phosphorylation; Fyn
资金
- National Institute of Neurological Disorders and Stroke [NS047478, NS048045, NS051195, NS056359, NS054900]
- Medical Research Council
- Wellcome Trust
- Maltz Family Foundation
- laboratory of Jasminka Godovac-Zimmermann (Rayne Institute, UCL, London)
Phosphorylation of GABA(A) receptors is an important mechanism for dynamically modulating inhibitory synaptic function in the mammalian brain. In particular, phosphorylation of tyrosine residues 365 and 367 (Y365/7) within the GABA(A) receptor gamma 2 subunit negatively regulates the endocytosis of GABA(A) receptors and enhances synaptic inhibition. Here we show that Fyn, a Src family kinase (SFK), interacts with the gamma 2 subunit in a phosphorylation-dependent manner. Furthermore, we demonstrate that Fyn binds within a region of the gamma 2 intracellular domain that is centered on residues Y365/7, with the phosphorylation of Y367 being particularly important for mediating this interaction. Tyrosine phosphorylation of the gamma 2 subunit is significantly reduced in the hippocampus of Fyn knockout mice, suggesting that Fyn is an important kinase that contributes to the phosphorylation of this subunit in vivo. Tyrosine phosphorylation of the gamma 2 subunit is not completely abolished in Fyn kinase mice, suggesting that other SFKs, such as Src, also contribute to maintaining and regulating the endogenous phosphorylation level of gamma 2-containing GABA(A) receptors. In summary, we demonstrate Fyn as one of the SFKs that binds to and phosphorylates the gamma 2 subunit of the GABA(A) receptor. This has important implications for the regulation of synaptic GABA(A) receptors via signaling pathways that lead to the activation of Fyn kinase. (C) 2010 Elsevier Inc. All rights reserved.
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