Role of Aquaporin-2 and TRPV4 in renal cell migration

BELTRAMONE N; CAPURRO C; RIVERA MF; FORD P; CUTRERA N; RIVAROLA V; DI GIUSTO G

CABA

Congreso; Reunion de Sociedades de Biociencias SAIC SAFIS SAI 2020; 2020

SAIC SAFIS SAI

We have previously shown that Aquaporin-2 (AQP2) promotes renal cell migration. This promigratory effect is due, at least in part, to the modulation of Na+/H+ exchanger (NHE1) activity, responsible for lamellipodia alkalinization, which would generate the appropriate microenvironment for actin and focal adhesion dynamics. Taking into account that we have demonstrated a physical and functional interaction between AQP2 and Ca2+ channel TRPV4, and that NHE1 activity is modulated by Ca2+, we propose to investigate the contribution of TRPV4 in the AQP2-dependent renal cell migration. We used two renal cell models: one WT not expressing AQPs and another one expressing AQP2. First, we determined TRPV4 expression in lamellipodia of migrating cells by immunofluorescence assays. Then, we evaluated TRPV4 participation in collective cell migration through wound healing assays in presence of a specific activator (GSK1016790A, 3nM). Finally, we characterize focal adhesion complexes by revealing the mechanosensor Vinculin. Our results showed that TRPV4 is present in lamellipodia of both cell types, but AQP2-expressing cells have a higher intensity ratio per area analyzed (WT: 794±84, n=32; AQP2: 1371±79, n=74; ***p