Paracellin-1 and the modulation of ion selectivity of tight junctions

Jianghui Hou, David L. Paul, Daniel A. Goodenough

Research output: Contribution to journalArticlepeer-review

192 Scopus citations


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+.

Original languageEnglish
Pages (from-to)5109-5118
Number of pages10
JournalJournal of cell science
Issue number21
StatePublished - Nov 1 2005


  • Hypomagnesemia
  • Ion selectivity
  • Paracellin-1
  • Tight junction


Dive into the research topics of 'Paracellin-1 and the modulation of ion selectivity of tight junctions'. Together they form a unique fingerprint.

Cite this