title: Targeting of the Arpc3 actin nucleation factor by miR-29a/b regulates dendritic spine morphology.
abstract: Previous studies have demonstrated that microribonucleic acids (miRs) are key regulators of protein expression in the brain and modulate dendritic spine morphology and synaptic activity. To identify novel miRs involved in neuronal plasticity, we exposed adult mice to chronic treatments with nicotine, cocaine, or amphetamine, which are psychoactive drugs that induce well-documented neuroadaptations. We observed brain region- and drug-specific changes in miR expression levels and identified miR-29a/b as regulators of synaptic morphology. In vitro imaging experiments indicated that miR-29a/b reduce mushroom-shaped dendritic spines on hippocampal neurons with a concomitant increase in filopodial-like outgrowths, suggesting an effect on synapse formation via actin cytoskeleton remodeling. We identified Arpc3, a component of the ARP2/3 actin nucleation complex, as a bona fide target for down-regulation by miR-29a/b. This work provides evidence that targeting of Arpc3 by miR-29a/b fine tunes structural plasticity by regulating actin network branching in mature and developing spines.
authors.affiliation: Medical Research Council Toxicology Unit, University of Leicester, Leicester, LE1 9HN, England, UK. glippi@ucsd.edu
authors.forename: Giordano
authors.initials: G
authors.lastname: Lippi
authors.forename: Joern R
authors.initials: JR
authors.lastname: Steinert
authors.forename: Emma L
authors.initials: EL
authors.lastname: Marczylo
authors.forename: Sabina
authors.initials: S
authors.lastname: D'Oro
authors.forename: Roberto
authors.initials: R
authors.lastname: Fiore
authors.forename: Ian D
authors.initials: ID
authors.lastname: Forsythe
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schratt
authors.forename: Michele
authors.initials: M
authors.lastname: Zoli
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Nicotera
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Young
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000235:genetics / Q000378:metabolism*; D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D006624:Hippocampus / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D014162:Transfection
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; C513333:Arpc3 protein, mouse; C547014:MIRN29 microRNA, mouse; D035683:MicroRNAs