The role of podocytes in glomerular permselectivity is tightly associated with their intricate morphology, featuring interdigitating foot processes from adjacent cells. The actin cytoskeleton is an integral component of podocyte foot processes and is regulated by a number of proteins expressed in podocytes. Rho-family of small GTPases are known key regulators of the actin cytoskeleton. This study, investigated the role of Rac1 in podocytes, using conditionally immortalized mouse podocytes (MPs). We studied Rho-GTPase activities and morphology/cytoskeleton of differentiating mouse podocytes stably expressing nephrin. We also studied the impact of transfection of various Rho-GTPase mutants and IQGAP1 mutants. We demonstrated that nephrin expression potentiates and sustains Rac1 activity during the differentiation process. We showed that Rac1 contributes to process formation in differentiating MPs and may have a similar role in vivo when podocytes are recovering from injuries.

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