Objective
The electrical excitability is a fundamental property of neurons. Diversity in intrinsic neuronal excitability is generated by the variable expression, subcellular localization, and function of a complex repertoire of ion channels. Dynamic regulation of intrinsic excitability can further alter the behavior of neurons and confer plasticity to neuronal signaling. Aberrant expression, localization, and function of ion channels can result in channel-based pathophysiologies. One of the challenging questions is to understand how neurons regulate the expression and localization of ion channels. The Axon Inital Segment (AIS) and the nodes of Ranvier are key sub-compartments that generate and conduct the action potentials along the axon. The voltage-dependent sodium (Nav) and potassium (Kv) channels are critically concentrated at the AIS and nodes of Ranvier to ensure proper axon potential propagation. Despite the central role of these channels in excitability, the molecular and cellular determinants governing their appropriate targeting and membrane organization are just beginning to emerge. An intricate assembly of adhesion molecules and cytoskeletal scaffold proteins hold Nav and Kv channels in place. However, how such a complex is dynamically regulated is still largely unknown. We recently identified two new processes based on phosphorylation of Nav and Kv complexes by two kinases, casein kinase 2 (CK2) and cyclin-dependant kinase (Cdks). The phosphorylation/dephosphorylation modifications of these channels modify indeed their localization at the AIS. Here, I propose to analyze, using a multidisciplinary approach, the respective role of CK2 and Cdks signaling pathways on dynamic targeting/assembly of Nav1 and Kv1 channels at the AIS and in the node of Ranvier. The end-results of this proposal should provide new insights into the mechanisms involved in the dynamic regulation of excitability and opens new paths to better understand defects leading to neuronal dysfunction.
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 biological sciences neurobiology
- natural sciences chemical sciences inorganic chemistry alkali metals
- medical and health sciences basic medicine physiology pathophysiology
- natural sciences biological sciences biochemistry biomolecules proteins
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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-IRG-2008
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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.
Coordinator
13284 Marseille
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.