La mucoviscidose et autres canalopathies

Summary: Mutations in cystic fibrosis transmembrane conductance regulator gene, CFTR, are responsible for cystic fibrosis, CF, a channelopathie. CFTR protein is a multifunctional protein with a main function of Cl− channel. CFTR is expressed in epithelia (upper airways, intestine, pancreas etc.). In the first part of this revue, we describe the main properties of CFTR underlying that it is not only a Cl− channel protein but also a multifunctional protein. We present a hypothesis which postulates that CFTR is a hub protein interacting with more than 140 proteins, and through these interactions regulates a number of functions which are abnormal in CF (ion transport, inflammation etc.). In the second part of the revue we briefly present a selection of other epithelial channelopathies due to mutations in genes of other Cl− or cation channels. Of note, these channels either interacts with CFTR or are considered as alternative channels in CF, and, as such, are targets for pharmacotherapies. We want to leave the reader with a message that to investigate channalopathies, to dissect the molecular mechanisms underlying channels’activity, allow not only to better understand basic mechanisms of channel regulation but in fine, to propose new targets for pharmacotherapies. [Copyright &y& Elsevier]