Paracellin-1, a Renal Tight Junction Protein Required for Paracellular Mg2+ Resorption

Science  02 Jul 1999:
Vol. 285, Issue 5424, pp. 103-106
DOI: 10.1126/science.285.5424.103

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Epithelia permit selective and regulated flux from apical to basolateral surfaces by transcellular passage through cells or paracellular flux between cells. Tight junctions constitute the barrier to paracellular conductance; however, little is known about the specific molecules that mediate paracellular permeabilities. Renal magnesium ion (Mg2+) resorption occurs predominantly through a paracellular conductance in the thick ascending limb of Henle (TAL). Here, positional cloning has identified a human gene,paracellin-1 (PCLN-1), mutations in which cause renal Mg2+ wasting. PCLN-1 is located in tight junctions of the TAL and is related to the claudin family of tight junction proteins. These findings provide insight into Mg2+homeostasis, demonstrate the role of a tight junction protein in human disease, and identify an essential component of a selective paracellular conductance.

  • * These authors contributed equally to this report.

  • To whom correspondence should be addressed. E-mail: richard.lifton{at}

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