RESUMO
Members of the claudin family of proteins are the main components of tight junctions (TJs), the major selective barrier of the paracellular pathway between epithelial cells. As such, the claudins have the ability to generate the TJ physiological barrier and to control various physiological processes. Therefore, the importance of this family of proteins is obvious and many efforts were made to reveal different aspects of claudin TJ protein biology. In this review, we discuss recent advances in our understanding of claudin structure and function, as well as their distribution pattern in different organs and tissues. We mainly highlight the complex interactions of claudins in various physiological systems and suggest a possible role for a coregulation mechanism.
Assuntos
Claudinas/metabolismo , Isoformas de Proteínas/metabolismo , Junções Íntimas/química , Junções Íntimas/metabolismo , Animais , Claudinas/química , Claudinas/genética , Humanos , Proteínas de Membrana/química , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Fenótipo , Conformação Proteica , Isoformas de Proteínas/química , Isoformas de Proteínas/genética , Distribuição TecidualRESUMO
Members of the claudin family of proteins are the main components of tight junctions (TJs), the major selective barrier of the paracellular pathway between epithelial cells. The selectivity and specificity of TJ strands are determined by the type of claudins present. An understanding of the cooperation between different claudins in various tissues is thus important. To study the possible cooperation between claudin 11 and claudin 14, we have generated claudin 11/claudin 14 double-deficient mice, which exhibit a combination of the phenotypes found in each of the singly deficient mutants, including deafness, neurological deficits, and male sterility. These two claudins have distinct and partially overlapping expression patterns in the kidney. Claudin 11 is located in both the proximal and distal convoluted tubules, whereas claudin 14 occurs in both the thin descending and thick ascending limbs of the loop of Henle and in the proximal convoluted tubules. Although daily urinary excretion of Mg(++), and to a lesser extent of Ca(++), tends to be higher in claudin 11/claudin 14 double mutants, these changes do not reach statistical significance compared with wild-type animals. Thus, under normal conditions, co-deletion of claudin 11 and claudin 14 does not affect kidney function or ion balance. Our data demonstrate that, despite the importance of each of these claudins, there is probably no functional cooperation between them. Generation of additional mouse models in which different claudins are abolished should provide further insight into the complex interactions between claudin proteins in various physiological systems.
