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This Article Full Text Full Text (PDF) All Versions of this Article: 295/2/F478    most recent 90226.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Torielli, L. Articles by Zurzolo, C. Search for Related Content PubMed PubMed Citation Articles by Torielli, L. Articles by Zurzolo, C.

-Adducin mutations increase Na/K pump activity in renal cells by affecting constitutive endocytosis: implications for tubular Na reabsorption

¹Prassis sigma tau Research Institute, Milan; ²Dipartimento di Biologia e Patologia Cellulare e Molecolare, ³Department of Clinical and Experimental Medicine, Federico II University of Naples, Naples; and ⁴Chair of Nephrology, Dialysis and Hypertension, Vita-Salute San Raffaele University, San Raffaele Hospital, Milan, Italy

Submitted 1 April 2008 ; accepted in final form 29 May 2008

Genetic variation in -adducin cytoskeletal protein is implicated in the polymerization and bundling of actin and alteration of the Na/K pump, resulting in abnormal renal sodium transport and hypertension in Milan hypertensive rats and humans. To investigate the molecular involvement of -adducin in controlling Na/K pump activity, wild-type or mutated rat and human -adducin forms were, respectively, transfected into several renal cell lines. Through multiple experimental approaches (microscopy, enzymatic assays, coimmunoprecipitation), we showed that rat and human mutated forms increased Na/K pump activity and the number of pump units; moreover, both variants coimmunoprecipitate with Na/K pump. The increased Na/K pump activity was not due to changes in its basolateral localization, but to an alteration of Na/K pump residential time on the plasma membrane. Indeed, both rat and human mutated variants reduced constitutive Na/K pump endocytosis and similarly affected transferrin receptor trafficking and fluid-phase endocytosis. In fact, -adducin was detected in clathrin-coated vesicles and coimmunoprecipitated with clathrin. These results indicate that adducin, besides its modulatory effects on actin cytoskeleton dynamics, might play a direct role in clathrin-dependent endocytosis. The constitutive reduction of the Na/K pump endocytic rate induced by mutated adducin variants may be relevant in Na-dependent hypertension.

hypertension; Na transport; clathrin; trafficking; immunoprecipitation