DCVFUSION

Telling the full story: how neurons send other signals than by classical synaptic transmission

Coordinatore	STICHTING VU-VUMC    more Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie.
Nazionalità Coordinatore	Netherlands [NL]
Totale costo	2˙439˙315 €
EC contributo	2˙439˙315 €
Programma	FP7-IDEAS-ERC Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	ERC-2012-ADG_20120314
Funding Scheme	ERC-AG
Anno di inizio	2013
Periodo (anno-mese-giorno)	2013-05-01   -   2018-04-30

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	STICHTING VU-VUMC  Organization address address: DE BOELELAAN 1105 city: AMSTERDAM postcode: 1081 HV contact info Titolo: Ms. Nome: Els Cognome: Borghols Email: send email Telefono: 31205986925	NL (AMSTERDAM)	hostInstitution	2˙439˙315.00
2	STICHTING VU-VUMC  Organization address address: DE BOELELAAN 1105 city: AMSTERDAM postcode: 1081 HV contact info Titolo: Prof. Nome: Matthijs Cognome: Verhage Email: send email Telefono: +31 20 5986936 Fax: +31 20 5986926	NL (AMSTERDAM)	hostInstitution	2˙439˙315.00

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 Obiettivo del progetto (Objective)

'The regulated secretion of chemical signals in the brain occurs principally from two organelles, synaptic vesicles and dense core vesicles (DCVs). Synaptic vesicle secretion accounts for the well characterized local, fast signalling in synapses. DCVs contain a diverse collection of cargo, including many neuropeptides that trigger a multitude of modulatory effects with quite robust impact, for instance on memory, mood, pain, appetite or social behavior. Disregulation of neuropeptide secretion is firmly associated with many diseases such as cognitive and mood disorders, obesity and diabetes. In addition, many other signals depend on DCVs, for instance trophic factors and proteolytic enzymes, but also signals that typically do not diffuse like guidance cues and pre-assembled active zones. Hence, it is beyond doubt that DCV signalling is a central factor in brain communication. However, many fundamental questions remain open on DCV trafficking and secretion. Therefore, the aim of this proposal is to characterize the molecular principles that account for DCV delivery at release sites and their secretion. I will address 4 fundamental questions: What are the molecular factors that drive DCV fusion in mammalian CNS neurons? How does Ca2 trigger DCV fusion? What are the requirements of DCV release sites and where do they occur? Can DCV fusion be targeted to synthetic release sites in vivo? I will exploit >30 mutant mouse lines and new cell biological and photonic approaches that allow for the first time a quantitative assessment of DCV-trafficking and fusion of many cargo types, in living neurons with a single vesicle resolution. Preliminary data suggest that DCV secretion is quite different from synaptic vesicle and chromaffin granule secretion. Together, these studies will produce the first systematic evaluation of the molecular identity of the core machinery that drives DCV fusion in neurons, the Ca2-affinity of DCV fusion and the characteristics of DCV release sites.'