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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.

Author information

  • 1EMBL, Mouse Biology Unit, Adriano Buzzati-Traverso Campus, Via Ramarini 32, 00015 Monterotondo, Italy.

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.

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