Article
- The EMBO Journal (2007) 26, 2991 - 3002
- doi:10.1038/sj.emboj.7601737
Published online: 31 May 2007
Subject Categories:
Profilin2 contributes to synaptic vesicle exocytosis, neuronal excitability, and novelty-seeking behavior
Pietro Pilo Boyl1,a, Alessia Di Nardo2,a, Christophe Mulle3, Marco Sassoè-Pognetto4, Patrizia Panzanelli4, Andrea Mele5, Matthias Kneussel6, Vivian Costantini5, Emerald Perlas1, Marzia Massimi1, Hugo Vara4, Maurizio Giustetto4 and Walter Witke1
- EMBL, Mouse Biology Unit, Monterotondo, Italy
- Childrens's Hospital, Department of Neurology, Boston, MA, USA
- UMR CNRS 5091, Institut François Magendie, Physiologie Cellulaire de la Synapse, Bordeaux, France
- Department of Anatomy, Pharmacology and Forensic Medicine and Istituto Nazionale di Neuroscienze, University of Turin, Torino, Italy
- Università di Roma 'La Sapienza', Laboratorio di Psicobiologia, Dipart. di Genetica e Biologia Molecolare, Roma, Italy
- Centre for Molecular Neurobiology, ZMNH, University of Hamburg, Hamburg, Germany
Correspondence to:
Walter Witke, EMBL, Mouse Biology Unit, Adriano Buzzati-Traverso Campus, Via Ramarini 32, 00015 Monterotondo, Italy. Tel.: +0039 06 90091 268; Fax: +0039 06 90091 272; E-mail: witke@embl-monterotondo.it
aThese authors contributed equally to this work
Received 21 December 2006; Accepted 3 May 2007
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.
Keywords:
- actin binding proteins,
- neurotransmitter release,
- profilin2,
- synaptic actin polymerization
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