Paracellin-1, a renal tight junction protein required for paracellular Mg2+ resorption.
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.
Simon
D B
DB
Howard Hughes Medical Institute, Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.
Lu
Y
Y
Choate
K A
KA
Velazquez
H
H
Al-Sabban
E
E
Praga
M
M
Casari
G
G
Bettinelli
A
A
Colussi
G
G
Rodriguez-Soriano
J
J
McCredie
D
D
Milford
D
D
Sanjad
S
S
Lifton
R P
RP
D000595:Amino Acid Sequence; D002118:Calcium / Q000652:urine; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D057167:Claudins; D003001:Cloning, Molecular; D005260:Female; D005808:Genes, Recessive; D006706:Homeostasis; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics* / Q000378:metabolism; D007684:Kidney Tubules / Q000737:chemistry; D008138:Loop of Henle / Q000737:chemistry / Q000378:metabolism*; D008274:Magnesium / Q000097:blood / Q000378:metabolism*; D008275:Magnesium Deficiency / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D020161:Physical Chromosome Mapping; D019108:Tight Junctions / Q000378:metabolism*
D057167:Claudins; D008565:Membrane Proteins; C502010:claudin 16; D008274:Magnesium; D002118:Calcium