Control of Epithelial Ion Transport by Cl- and PDZ Proteins
Overview
Authors
Affiliations
Inhibition of epithelial Na+ channels (ENaC) by the cystic fibrosis transmembrane conductance regulator (CFTR) has been demonstrated previously. Recent studies suggested a role of cytosolic Cl- for the interaction of CFTR with ENaC, when studied in Xenopus oocytes. In the present study we demonstrate that the Na+ / H+ -exchanger regulator factor (NHERF) controls expression of CFTR in mouse collecting duct cells. Inhibition of NHERF largely attenuates CFTR expression, which is paralleled by enhanced Ca(2+) -dependent Cl- secretion and augmented Na+ absorption by the ENaC. It is further demonstrated that epithelial Na+ absorption and ENaC are inhibited by cytosolic Cl- and that stimulation by secretagogues enhances the intracellular Cl- concentration. Thus, the data provide a clue to the question, how epithelial cells can operate as both absorptive and secretory units: Increase in intracellular Cl- during activation of secretion will inhibit ENaC and switch epithelial transport from salt absorption to Cl- secretion.
Schreiber R, Ousingsawat J, Wanitchakool P, Sirianant L, Benedetto R, Reiss K J Physiol. 2017; 596(2):217-229.
PMID: 29134661 PMC: 5767690. DOI: 10.1113/JP275175.
Shank2 mutant mice display a hypersecretory response to cholera toxin.
Jung E, Park J, Gee H, Jung J, Noh S, Lee J J Physiol. 2014; 592(8):1809-21.
PMID: 24445315 PMC: 4001754. DOI: 10.1113/jphysiol.2013.268631.
TRPM7 is regulated by halides through its kinase domain.
Yu H, Zhang Z, Lis A, Penner R, Fleig A Cell Mol Life Sci. 2013; 70(15):2757-71.
PMID: 23471296 PMC: 3710292. DOI: 10.1007/s00018-013-1284-6.
Ion channel function of aquaporin-1 natively expressed in choroid plexus.
Boassa D, Stamer W, Yool A J Neurosci. 2006; 26(30):7811-9.
PMID: 16870726 PMC: 6674226. DOI: 10.1523/JNEUROSCI.0525-06.2006.
Adam G, Ousingsawat J, Schreiber R, Kunzelmann K Pflugers Arch. 2004; 449(5):470-8.
PMID: 15517342 DOI: 10.1007/s00424-004-1356-4.