title: Actinin-4 Governs Dendritic Spine Dynamics and Promotes Their Remodeling by Metabotropic Glutamate Receptors.
abstract: Dendritic spines are dynamic, actin-rich protrusions in neurons that undergo remodeling during neuronal development and activity-dependent plasticity within the central nervous system. Although group 1 metabotropic glutamate receptors (mGluRs) are critical for spine remodeling under physiopathological conditions, the molecular components linking receptor activity to structural plasticity remain unknown. Here we identify a Ca(2+)-sensitive actin-binding protein, α-actinin-4, as a novel group 1 mGluR-interacting partner that orchestrates spine dynamics and morphogenesis in primary neurons. Functional silencing of α-actinin-4 abolished spine elongation and turnover stimulated by group 1 mGluRs despite intact surface receptor expression and downstream ERK1/2 signaling. This function of α-actinin-4 in spine dynamics was underscored by gain-of-function phenotypes in untreated neurons. Here α-actinin-4 induced spine head enlargement, a morphological change requiring the C-terminal domain of α-actinin-4 that binds to CaMKII, an interaction we showed to be regulated by group 1 mGluR activation. Our data provide mechanistic insights into spine remodeling by metabotropic signaling and identify α-actinin-4 as a critical effector of structural plasticity within neurons.
authors.affiliation: From the Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kalinowska
authors.affiliation: From the Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461.
authors.forename: Andrés E
authors.initials: AE
authors.lastname: Chávez
authors.affiliation: From the Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461.
authors.forename: Stefano
authors.initials: S
authors.lastname: Lutzu
authors.affiliation: From the Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461.
authors.forename: Pablo E
authors.initials: PE
authors.lastname: Castillo
authors.affiliation: From the Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461.
authors.forename: Feliksas F
authors.initials: FF
authors.lastname: Bukauskas
authors.affiliation: From the Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461 anna.francesconi@einstein.yu.edu.
authors.forename: Anna
authors.initials: A
authors.lastname: Francesconi
mesh_terms: D000185:Actinin / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D011485:Protein Binding; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism*
chemical_list: C111453:ACTN4 protein, human; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D000185:Actinin; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2
keywords: Ca2+/calmodulin-dependent protein kinase II (CaMKII); actin-binding proteins; actinin; dendritic protrusion dynamics; dendritic spine; metabotropic glutamate receptor (mGluR); neuron; synaptic plasticity