AUTHOR=Mao Li-Min , Young Lexi , Chu Xiang-Ping , Wang John Q. 

TITLE=Regulation of Src family kinases by muscarinic acetylcholine receptors in heterologous cells and neurons

JOURNAL=Frontiers in Molecular Neuroscience

VOLUME=16

YEAR=2024

URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2023.1340725

DOI=10.3389/fnmol.2023.1340725

ISSN=1662-5099

ABSTRACT=<p>Five muscarinic acetylcholine (mACh) receptor subtypes are divided into two classes: the M1 class (M<sub>1</sub>, M<sub>3</sub>, and M<sub>5</sub>) and the M2 class (M<sub>2</sub> and M<sub>4</sub>). The former is coupled to G<sub>q</sub> proteins, while the latter is coupled to G<sub>i/o</sub> proteins. Accumulating evidence indicates that mACh receptors play a significant role in the regulation of the Src family kinase (SFK), a subfamily of non-receptor tyrosine kinases. mACh receptors exert their roles in a subtype-dependent fashion and preferentially target Src and Fyn, two members of SFKs that are expressed in the brain and enriched at synaptic sites. While the M<sub>1</sub> receptor positively modulates SFK activity, the M<sub>4</sub> receptor inhibits it. By modulating SFKs, mACh receptors are actively involved in the regulation of expression and function of a variety of receptors, structural proteins, and signaling molecules. In particular, the M<sub>4</sub> receptor and the dopamine D<sub>1</sub> receptor are coexpressed in striatonigral projection neurons of the striatum. G<sub>i/o</sub>-coupled M<sub>4</sub> and G<sub>q</sub>-coupled D<sub>1</sub> receptors antagonistically regulate SFK activity, thereby forming a dynamic balance controlling glutamate receptor activity, excitability of neurons, and synaptic plasticity. In summary, mACh receptors play a crucial role in regulating SFK activity in heterologous cells and neurons.</p>