title: Profilin2 contributes to synaptic vesicle exocytosis, neuronal excitability, and novelty-seeking behavior.
abstract: Profilins are actin binding proteins essential for regulating cytoskeletal dynamics, however, their function in the mammalian nervous system is unknown. Here, we provide evidence that in mouse brain profilin1 and profilin2 have distinct roles in regulating synaptic actin polymerization with profilin2 preferring a WAVE-complex-mediated pathway. Mice lacking profilin2 show a block in synaptic actin polymerization in response to depolarization, which is accompanied by increased synaptic excitability of glutamatergic neurons due to higher vesicle exocytosis. These alterations in neurotransmitter release correlate with a hyperactivation of the striatum and enhanced novelty-seeking behavior in profilin2 mutant mice. Our results highlight a novel, profilin2-dependent pathway, regulating synaptic physiology, neuronal excitability, and complex behavior.
authors.affiliation: EMBL, Mouse Biology Unit, Adriano Buzzati-Traverso Campus, Via Ramarini 32, 00015 Monterotondo, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Pilo Boyl
authors.forename: Alessia
authors.initials: A
authors.lastname: Di Nardo
authors.forename: Christophe
authors.initials: C
authors.lastname: Mulle
authors.forename: Marco
authors.initials: M
authors.lastname: Sassoè-Pognetto
authors.forename: Patrizia
authors.initials: P
authors.lastname: Panzanelli
authors.forename: Andrea
authors.initials: A
authors.lastname: Mele
authors.forename: Matthias
authors.initials: M
authors.lastname: Kneussel
authors.forename: Vivian
authors.initials: V
authors.lastname: Costantini
authors.forename: Emerald
authors.initials: E
authors.lastname: Perlas
authors.forename: Marzia
authors.initials: M
authors.lastname: Massimi
authors.forename: Hugo
authors.initials: H
authors.lastname: Vara
authors.forename: Maurizio
authors.initials: M
authors.lastname: Giustetto
authors.forename: Walter
authors.initials: W
authors.lastname: Witke
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D005089:Exocytosis / Q000502:physiology*; D007858:Learning; D017774:Long-Term Potentiation; D008568:Memory; D051379:Mice; D009474:Neurons / Q000502:physiology*; D051304:Profilins / Q000502:physiology*
chemical_list: C495742:Pfn2 protein, mouse; D051304:Profilins