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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

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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.

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CABELLO, Nuria, REMELLI, Rosaria, CANELA, Laia, SORIGUERA, Ana, MALLOL MONTERO, Josefa, CANELA CAMPOS, Enric i. (enric isidre), ROBBINS, Melanie j., LLUÍS I BISET, Carme, FRANCO FERNÁNDEZ, Rafael, MCILHINNEY, R. a. jeffrey, CIRUELA ALFÉREZ, Francisco. 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. _Journal of Biological Chemistry_. 2007. Vol. 282, núm. 16, pàgs. 12143-12153. [consulta: 22 de febrer de 2026]. ISSN: 0021-9258. [Disponible a: https://hdl.handle.net/2445/122383]

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