Objective
T-lymphocytes require calcium entry though the plasma membrane for their activation and function. Recently, several routes for calcium entry through the T cell plasma membrane after activation have been described. These include CRAC channels (Calcium Release of Activated Channels), TRP channels (Transient Receptor Potential) and inositol-1,4,5-trisphosphate receptors (IP3R). Herein we are proposing the emergence of a new fourth route for calcium entry, composed of Cav channels (also known as L-type voltage gated calcium channels) and their regulator scaffold protein AHNAK1 (AHNAK/Desmoyokin). In excitable cells, such as neurons or muscle cells, Cav calcium channels constitute the major route for calcium entry. We have previously published that both helper (CD4+) and killer (CD8+) T cells express high levels of Cav1 alpha1 subunits (alpha 1S, -1C, -1D and -1F) and AHNAK1 after their differentiation and require these molecules for calcium entry during an immune response.
This proposal aims to study the molecular mechanism by which this pathway is induced and functions. My preliminary evidence suggest that Cav channel calcium currents are induced by TCR stimulation, not by voltage depolarization, as described in excitable cells. Further studies proposed here are required to study this phenomenon.
In this proposal, we will describe the observations and open questions, which ultimately suggests the involvement of multiple consecutive routes for calcium entry into lymphocytes, one of which is apparently mediated by Cav channels and AHNAK1.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences chemical sciences inorganic chemistry alkaline earth metals
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine immunology
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
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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
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2010-RG
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Funding Scheme
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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.
Coordinator
91120 Jerusalem
Israel
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