Objective
The epithelial Na+ channel (ENaC) plays a major role in the homeostasis of extracellular Na+ and consequently of blood volume and pressure. Its importance is underlined by its genetic linkage to two renal diseases, pseudohypoaldosteronism type I, and of Li ddle¿s syndrome, which are both caused by mutations in the genes encoding ENaC. ENaC, which facilitates entry of Na+ into the cell, is the rate-limiting step of Na+ reabsorption. It is highly regulated by a variety of factors, including aldosterone and vas opressin, but the molecular mechanisms of their action are still poorly understood. Aldosterone induces and/or represses a number of genes, which consequently lead to the stimulation of transepithelial transport. We have identified a novel protein, NDRG2 ( N-myc Downstream Regulated Gene 2) whose expression is very early stimulated by aldosterone, both in established cell lines, and in the kidney and colon of rats. NDRG2 belongs to a family of genes of unknown function, which is conserved in plants, inverteb rates and mammals, suggesting important functions. Its identity with MESK2, a gene recently identified in Drosophila, suggests that it may be involved in the Ras/MAPK signaling pathway. Our preliminary data suggest that aldosterone does influence Ras activ ity, and co-expression of NDRG2 with ENaC into Xenopus laevis oocytes elevates ENaC activity as compared to control oocytes. My project will be focussed on the analysis of NDRG2 function, in cell cultures, and in vivo by transgenesis. We will use condition al systems (tet inducible and HoxB7 promotor kidney-targeting in mice, Tamoxifen-sensitive Cre-Lox in cells) to evaluate the consequences of NDRG2 overexpression on renal collecting duct differentiation, polarity and sodium transport capacities. Constructs have been made, cell transfection is in progress and mouse generation will be initiated in March 2004. We will search for alterations in sodium transport after NDRG2 overexpression.
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 chemical sciences inorganic chemistry alkali metals
- medical and health sciences clinical medicine nephrology
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences zoology mammalogy
- medical and health sciences basic medicine physiology homeostasis
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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.
FP6-2002-MOBILITY-5
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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
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.