Actin-binding protein α-actinin-1 interacts with the metabotropic glutamate receptor type 5b and modulates the cell surface expression and function of the receptor

Abstract

Receptors for neurotransmitters require scaffolding proteins for membrane microdomain targeting and for regulating receptor function. Using a yeast two-hybrid screen, α-actinin-1, a major F-actin cross-linking protein, was identified as a binding partner for the C-terminal domain of metabotropic glutamate receptor type 5b (mGlu5b receptor). Co-expression, co-immunoprecipitation, and pull-down experiments showed a close and specific interaction between mGlu5b receptor and α-actinin-1 in both transfected HEK-293 cells and rat striatum. The interaction of α-actinin-1 with mGlu5b receptor modulated the cell surface expression of the receptor. This was dependent on the binding of α-actinin-1 to the actin cytoskeleton. In addition, the α-actinin-1/mGlu5b receptor interaction regulated receptor-mediated activation of the mitogen-activated protein kinase pathway. Together, these findings indicate that there is an α-actinin-1-dependent mGlu5b receptor association with the actin cytoskeleton modulating receptor cell surface expression and functioning.