title: Actin-binding protein alpha-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, alpha-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 (mGlu(5b) receptor). Co-expression, co-immunoprecipitation, and pull-down experiments showed a close and specific interaction between mGlu(5b) receptor and alpha-actinin-1 in both transfected HEK-293 cells and rat striatum. The interaction of alpha-actinin-1 with mGlu(5b) receptor modulated the cell surface expression of the receptor. This was dependent on the binding of alpha-actinin-1 to the actin cytoskeleton. In addition, the alpha-actinin-1/mGlu(5b) receptor interaction regulated receptor-mediated activation of the mitogen-activated protein kinase pathway. Together, these findings indicate that there is an alpha-actinin-1-dependent mGlu(5b) receptor association with the actin cytoskeleton modulating receptor cell surface expression and functioning.
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer and Department of Biochemistry and Molecular Biology, University of Barcelona, Facultat de Biologia, Avda. Diagonal 645, Barcelona 08028, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Cabello
authors.forename: Rosaria
authors.initials: R
authors.lastname: Remelli
authors.forename: Laia
authors.initials: L
authors.lastname: Canela
authors.forename: Ana
authors.initials: A
authors.lastname: Soriguera
authors.forename: Josefa
authors.initials: J
authors.lastname: Mallol
authors.forename: Enric I
authors.initials: EI
authors.lastname: Canela
authors.forename: Melanie J
authors.initials: MJ
authors.lastname: Robbins
authors.forename: Carme
authors.initials: C
authors.lastname: Lluis
authors.forename: Rafael
authors.initials: R
authors.lastname: Franco
authors.forename: R A Jeffrey
authors.initials: RA
authors.lastname: McIlhinney
authors.forename: Francisco
authors.initials: F
authors.lastname: Ciruela
mesh_terms: D000185:Actinin / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D000199:Actins; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D000185:Actinin