| First Author | Hou J | Year | 2005 |
| Journal | J Cell Sci | Volume | 118 |
| Issue | Pt 21 | Pages | 5109-18 |
| PubMed ID | 16234325 | Mgi Jnum | J:102389 |
| Mgi Id | MGI:3607439 | Doi | 10.1242/jcs.02631 |
| Citation | Hou J, et al. (2005) Paracellin-1 and the modulation of ion selectivity of tight junctions. J Cell Sci 118(Pt 21):5109-18 |
| abstractText | Tight junctions play a key selectivity role in the paracellular conductance of ions. Paracellin-1 is a member of the tight junction claudin protein family and mutations in the paracellin-1 gene cause a human hereditary disease, familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) with severe renal Mg2+ wasting. The mechanism of paracellin-1 function and its role in FHHNC are not known. Here, we report that in LLC-PK1 epithelial cells paracellin-1 modulated the ion selectivity of the tight junction by selectively and significantly increasing the permeability of Na+ (with no effects on Cl-) and generated a high permeability ratio of Na+ to Cl-. Mutagenesis studies identified a locus of amino acids in paracellin-1 critical for this function. Mg2+ flux across cell monolayers showed a far less-pronounced change (compared to monovalent alkali cations) following exogenous protein expression, suggesting that paracellin-1 did not form Mg2+-selective paracellular channels. We hypothesize that in the thick ascending limb of the nephron, paracellin-1 dysfunction, with a concomitant loss of cation selectivity, could contribute to the dissipation of the lumen-positive potential that is the driving force for the reabsorption of Mg2+. |
