Aquaporin-2 and Na+/H+ exchanger isoform 1 modulate the efficiency of renal cell migration.

VALERIA RIVAROLA; PAULA FORD; ALEJANDRO PIZZONI; ALAN WHITE; GISELA DI GIUSTO; NATALIA BELTRAMONE; CLAUDIA CAPURRO; VALERIA RIVAROLA; PAULA FORD; ALEJANDRO PIZZONI; ALAN WHITE; GISELA DI GIUSTO; NATALIA BELTRAMONE; CLAUDIA CAPURRO

JOURNAL OF CELLULAR PHYSIOLOGY

WILEY-LISS, DIV JOHN WILEY & SONS INC

Año: 2019 p. 4443 - 4454

0021-9541

Aquaporin-2 (AQP2) promotes renal cell migration by the modulation of integrin β1 trafficking and the turnover of focal adhesions. The aim of our work was to investigate whether AQP2 also works in cooperation with Na+/H+ exchanger isoform 1 (NHE1), another well-known protein involved in the regulation of cell migration. Our results showed that lamellipodia of AQP2-expressing cells exhibit significantly smaller volumes and areas of focal adhesions and more alkaline pHi due to increased NHE1 activity than AQP2-null cells. The blockage of AQP2, or its physically-associated calcium channel TRPV4, significantly reduced lamellipodia NHE1 activity. NHE1 blockage significantly reduced the rate of cell migration, the number of lamellipodia, and the assembly of F-actin only in AQP2-expressing cells. Our data suggest that AQP2 modulates the activity of NHE1 through its calcium channel partner TRPV4, thereby determining pH-dependent actin polymerization, providing mechanical stability to delineate lamellipodia structure and defining the efficiency of cell migration.