Abstract
Claudins are integral proteins expressed at the tight junctions of epithelial and endothelial cells. In the mammalian kidney, every tubular segment express a specific set of claudins that give to that segment unique properties regarding permeability and selectivity of the paracellular pathway. So far, 3 claudins (10b, 16 and 19) have been causally traced to rare human syndromes: variants of CLDN10b cause HELIX syndrome and variants of CLDN16 or CLDN19 cause familial hypomagnesemia with hypercalciuria and nephrocalcinosis. The review summarizes our current knowledge on the physiology of mammalian tight junctions and paracellular ion transport, as well as on the role of the 3 above-mentioned claudins in health and disease. Claudin 14, although not having been causally linked to any rare renal disease, is also considered, because available evidence suggests that it may interact with claudin 16. Some single-nucleotide polymorphisms of CLDN14 are associated with urinary calcium excretion and/or kidney stones. For each claudin considered, the pattern of expression, the function and the human syndrome caused by pathogenic variants are described.
Highlights
Almost every epithelium in multicellular organisms separates two compartments with differing ion composition
Based on the results described above, a consensual agreement is that the specific effect of claudin 10b is to increase the paracellular permeability to Na+
Claudin 16, Claudin 19 and Familial Hypomagnesemia with Hypercalciuria and Familial hypomagnesemia with hypercalciuria and nephrocalcinosis is an autosomal recessive disorder caused by variants of the CLDN16 (OMIM #248250) and CLDN19 (OMIM #248190) genes
Summary
Almost every epithelium in multicellular organisms separates two compartments (apical and basolateral) with differing ion composition. Passive diffusion between 2 compartments may be defined as the flow of solute that occurs in response to the difference in electrochemical potentials of the considered solute between both compartments. Because of the existing transmembrane electrochemical potential differences, sodium (Na+ ), calcium (Ca2+ ) and magnesium (Mg2+ ) cannot cross passively both apical and basolateral membranes: at some step, transcellular transport of Na+ , Ca2+. The present review is a summary of our knowledge of normal and abnormal paracellular ion transport in the mammalian renal tubule. It focuses on the role of claudin proteins, which are highly specialized proteins expressed at the tight junction, in health and disease
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