REDISTRIBUTION OF VILLIN TO PROXIMAL TUBULE BASOLATERAL MEMBRANES AFTER ISCHEMIA AND REPERFUSION

After ischemia and reperfusion, severe alterations in the cytoskeletal organization of renal tubular epithelial cells have been reported. Th ese effects, accompanied by a modification in the polarized distributi on of some membrane transport proteins, are especially evident in the proximal tubule. In normal proximal tubule cells, actin is concentrate d in apical brush border microvilli, along with the actin-binding prot ein villin. Because villin plays an important role in actin bundling a nd in microvillar assembly but can also act as an actin-fragmenting pr otein at higher calcium concentrations, we examined the effects of isc hemic injury and reperfusion on the distribution of villin and actin i n proximal tubule cells of rat kidney. Using specific antibodies again st villin and actin, we show that these proteins redistribute in paral lel from the apical to the basolateral plasma membrane within 1 h of r eperfusion after ischemia. Ischemia alone had no effect on the stainin g pattern. Repolarization of villin to the apical membrane begins with in hours after reperfusion with enhanced apical localization over time during the period of regeneration. This apical repolarization of vill in is accompanied by the migration of actin back to the apical membran e. These results show not only that villin may be involved in the init ial disruption of the actin cytoskeleton during reperfusion injury but also that its migration back to the apical domain of these cells acco mpanies the reestablishment of a normal actin distribution in the brus h border.