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| Subject Categories: Cell & Tissue Architecture | Neuroscience |
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| The EMBO Journal
(2007) 26, 2991–3002, doi:10.1038/sj.emboj.7601737 Published online 31 May 2007 |
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| Profilin2 contributes to synaptic vesicle exocytosis, neuronal excitability, and novelty-seeking behavior |
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| Pietro Pilo Boyl1, 7, Alessia Di Nardo2, 7, Christophe Mulle3, Marco Sassoè-Pognetto4, Patrizia Panzanelli4, Andrea Mele5, Matthias Kneussel6, Vivian Costantini5, Emerald Perlas1, Marzia Massimi1, Hugo Vara4, Maurizio Giustetto4 and Walter Witke1 |
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1 EMBL, Mouse Biology Unit, Monterotondo, Italy 2 Childrens's Hospital, Department of Neurology, Boston, MA, USA 3 UMR CNRS 5091, Institut François Magendie, Physiologie Cellulaire de la Synapse, Bordeaux, France 4 Department of Anatomy, Pharmacology and Forensic Medicine and Istituto Nazionale di Neuroscienze, University of Turin, Torino, Italy 5 Università di Roma 'La Sapienza', Laboratorio di Psicobiologia, Dipart. di Genetica e Biologia Molecolare, Roma, Italy 6 Centre for Molecular Neurobiology, ZMNH, University of Hamburg, Hamburg, Germany To whom correspondence should be addressed 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 7 These authors contributed equally to this work Received 21 December 2006; Accepted 3 May 2007; Published online 31 May 2007. |
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| Abstract |
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| 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. |
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| Keywords: actin binding proteins, neurotransmitter release, profilin2, synaptic actin polymerization |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated NEWS AND VIEWSNature Neuroscience News and Views (01 Feb 2003) Moving molecules make synapses Nature Neuroscience News and Views (01 Oct 2001) RESEARCHThe EMBO Journal Article Activity-induced targeting of profilin and stabilization of dendritic spine morphology Nature Neuroscience Article (01 Nov 2003) |
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