Control of cell migration and shape by dual water and ion conducting aquaporin channels
University of Adelaide, SA 5005.
Structure-function analyses of human aquaporin-1 (AQP1) channels are defining the gating mechanisms and permeation pathways of these intriguing dual water- and ion-conducting channels, and identifying new pharmacological agents that differentially regulate the parallel ion and water pores. The AQP1 ion conductance is necessary for rapid migration in subtypes of aggressive cancer cells. A photoswitchable cation sensing probe developed by our team allows real-time imaging to localise AQP1-mediated cation entry in migrating cells. An arylsulfonamide agent AqB011 designed by our group selectively blocks the ion channel of AQP1 (IC50 14 μM) without altering water permeability (at doses up to 200 μM), providing a key tool for analysing the physiological roles of the AQP1 cation channel conductance in the ability of cells to move and maintain proper shape, in processes important for development, repair and survival in multicellular organisms.