Profilin2 contributes to synaptic vesicle exocytosis, neuronal excitability, and novelty-seeking behavior.
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.
Pilo Boyl
Pietro
P
EMBL, Mouse Biology Unit, Adriano Buzzati-Traverso Campus, Via Ramarini 32, 00015 Monterotondo, Italy.
Di Nardo
Alessia
A
Mulle
Christophe
C
Sassoè-Pognetto
Marco
M
Panzanelli
Patrizia
P
Mele
Andrea
A
Kneussel
Matthias
M
Costantini
Vivian
V
Perlas
Emerald
E
Massimi
Marzia
M
Vara
Hugo
H
Giustetto
Maurizio
M
Witke
Walter
W
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*
C495742:Pfn2 protein, mouse; D051304:Profilins