ERPMCONTACTS

"Biochemical and functional characterization of ER-plasma membrane contact sites mediated by a novel class of tethering proteins, the Extended-Synaptotagmins"

Coordinatore	CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE    more  Organization address address: Rue Michel -Ange 3 city: PARIS postcode: 75794 contact info Titolo: Ms. Nome: Julie Cognome: Zittel Email: send email Telefono: +33 1 42349417
Nazionalità Coordinatore	France [FR]
Totale costo	100˙000 €
EC contributo	100˙000 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2013-CIG
Funding Scheme	MC-CIG
Anno di inizio	2014
Periodo (anno-mese-giorno)	2014-03-01   -   2018-02-28

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE  Organization address address: Rue Michel -Ange 3 city: PARIS postcode: 75794 contact info Titolo: Ms. Nome: Julie Cognome: Zittel Email: send email Telefono: +33 1 42349417	FR (PARIS)	coordinator	100˙000.00

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 Obiettivo del progetto (Objective)

'Endoplasmic reticulum (ER)-plasma membrane (PM) contact sites are structures where the ER is tightly associated with the PM. Most available information on ER-PM contacts in cells of higher eukaryotes concerns proteins implicated in the regulation of Ca2 entry. However, growing evidence suggests that such contacts play more general and conserved roles in cell physiology. I recently discovered that the three Extended-Synaptotagmins (E-Syts), which are orthologues of yeast tricalbins, are ER-resident proteins that act as regulated tethers between the ER and the PM. My studies revealed that E-Syts are essentially localized to sites of close apposition of ER and PM and their overexpression induces massive formation of cortical ER. In contrast, their loss of function affects formation of pre-existing ER-PM contacts but not capacitative Ca2 entry, indicating that E-Syts represent a novel class of ER-PM tethers with novel functions. Their binding to the PM is regulated by the PM phosphoinositide PI(4,5)P2. We hypothesize that one key function of E-Syt-mediated ER-PM contacts is regulation of PM phosphoinositide (PI) metabolism. The central objective of this proposal is to identify E-Syt binding partners and to understand their functions at ER-PM contact sites. Interestingly, the host group has identified the v-SNARE Sec22 as a novel component of ER-PM contact sites. In parallel to the well-studied synaptotagmin-SNARE complex at the synapse, it will be interesting to address whether E-Syts might be part of a non-fusogenic SNARE complex at ER-PM contact sites. A multidisciplinary approach will be taken using a combination of super-resolution light and electron microscopy, live-cell imaging and optogenetic manipulation of PIs in mammalian cells, coupled with biochemistry and in vitro reconstitution. These approaches will unravel the function of the newly discovered E-Syt proteins at ER-PM contacts, and how they interface with SNAREs at these sites to regulate PI signaling.'