Profilin2 contributes to synaptic vesicle exocytosis, neuronal excitability, and novelty-seeking behavior.

Pietro Pilo Boyl, Alessia Di Nardo, Christophe Mulle, Marco Sassoè-Pognetto, Patrizia Panzanelli, Andrea Mele, Matthias Kneussel, Vivian Costantini, Emerald Perlas, Marzia Massimi, Hugo Vara, Maurizio Giustetto, Walter Witke
EMBO J. 2007-05-31; 26(12): 2991-3002
DOI: 10.1038/sj.emboj.7601737

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1. EMBO J. 2007 Jun 20;26(12):2991-3002. Epub 2007 May 31.

Profilin2 contributes to synaptic vesicle exocytosis, neuronal excitability, and
novelty-seeking behavior.

Pilo Boyl P(1), Di Nardo A, Mulle C, Sassoè-Pognetto M, Panzanelli P, Mele A,
Kneussel M, Costantini V, Perlas E, Massimi M, Vara H, Giustetto M, Witke W.

Author information:
(1)EMBL, Mouse Biology Unit, Adriano Buzzati-Traverso Campus, Via Ramarini 32,
00015 Monterotondo, Italy.

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.

DOI: 10.1038/sj.emboj.7601737
PMCID: PMC1894775
PMID: 17541406 [Indexed for MEDLINE]

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