CRC 629 A06 - Regulation of cell elasticity and paracellular resistance by CFTR clusters

Basic data for this project

Description

In epithelia CFTR (cystic fibrosis transmembrane conductance regulator) maintains salt and fluid balance. Loss of CFTR function results in the severe disease, namely cystic fibrosis (CF). It is the most common genetic disease in Caucasians characterized by impaired epithelial transport mainly in the respiratory system, pancreas and liver. CFTR is a chloride channel and a regulator of several membrane conductances and cellular functions e.g. cell volume regulation. Upon stimulation with cAMP raising agents CFTR is inserted in the plasma membrane. There, CFTR forms clusters by multimerization and intracellular binding of several proteins. Such supramolecular CFTR clusters interact with the cytoskeleton and with other CFTR-controlled membrane proteins. Activated CFTR conducts chloride to the luminal side of the epithelium. This is the driving force for the paracellular transport of sodium into the lumen. In the leaky respiratory epithelium water follows mainly paracellular and, to a less extent, transcellular. Recent experiments in our lab led to the hypothesis that normal mechanical deformability of the cell (elasticity) and transepithelial permeability depend upon the presence of CFTR clusters in the plasma membrane. This proposal is supported by the finding , that the AMP dependent kinase AMPK-_1 and the proteinkinase CK2 are parts of supramolecular CFTR clusters.