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Profilin2 contributes to synaptic vesicle exocytosis, neuronal excitability, and novelty‐seeking behavior
Author(s) -
Pilo Boyl Pietro,
Di Nardo Alessia,
Mulle Christophe,
SassoèPognetto Marco,
Panzanelli Patrizia,
Mele Andrea,
Kneussel Matthias,
Costantini Vivian,
Perlas Emerald,
Massimi Marzia,
Vara Hugo,
Giustetto Maurizio,
Witke Walter
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601737
Subject(s) - biology , exocytosis , munc 18 , synaptic vesicle , novelty , neuroscience , synapsin , vesicle fusion , vesicle , microbiology and biotechnology , secretion , biochemistry , membrane , philosophy , theology
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.