Chapter 7 - Claudins and Renal Magnesium Handling

Abstract

Publisher Summary Claudins are tight junction (TJ) integral membrane proteins that are key regulators of the paracellular pathway. Defects in claudin-16 (CLDN16) and claudin-19 (CLDN19) function result in the inherited human renal disorder familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC). Significant advances have been made toward understanding the mechanisms underlying the roles of these claudins in mediating paracellular ion reabsorption in the kidney. This chapter reviews the biosynthesis, trafficking, and interaction of CLDN16 and CLDN19 molecules; the biophysical properties of CLDN16 and CLDN19 channels; and the pathogenic mechanisms for the role of mutant forms of CLDN16 and CLDN19 in the development of FHHNC. FHHNC is a genetically heterogeneous disorder. Mutations in TJ gene encoding CLDN19 are also linked to this disease. The renal tubular phenotypes are indistinguishable of patients with mutations in CLDN16 from those with CLDN19. CLDN19 mutations are invariably associated with severe ocular abnormalities. This association has been named FHHNC with severe ocular involvement.