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- Title
Profilin2 contributes to synaptic vesicle exocytosis, neuronal excitability, and novelty-seeking behavior.
- Authors
Pilo Boyl, Pietro; Di Nardo, Alessia; Mulle, Christophe; Sassoè-Pognetto, Marco; Panzanelli, Patrizia; Mele, Andrea; Kneussel, Matthias; Costantini, Vivian; Perlas, Emerald; Massimi, Marzia; Vara, Hugo; Giustetto, Maurizio; Witke, Walter
- 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.
- Subjects
SYNAPSES; EXOCYTOSIS; NEURONS; ACTIN; CARRIER proteins; NERVOUS system; POLYMERS
- Publication
EMBO Journal, 2007, Vol 26, Issue 12, p2991
- ISSN
0261-4189
- Publication type
Article
- DOI
10.1038/sj.emboj.7601737