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.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences physical sciences optics microscopy super resolution microscopy
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences physical sciences optics microscopy electron microscopy
- medical and health sciences basic medicine physiology
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2013-CIG
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Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
MC-CIG - Support for training and career development of researcher (CIG)
Coordinator
75794 PARIS
France
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.