Knock down of AQP1 in HMEC-1 and WM115 cells changes the organization of the cytoskeleton

Aquaporins are a family of water membrane-channel proteins expressed in diverse tissues. Recently AQP1 has been proposed as a novel promoter of tumor angiogenesis. Herein, we focused in particular on AQP1 investigating its role in both (HMEC-1) and in a human melanoma cell line (WM115). AQP-1 knock down by RNAi, affects cell shape determining a rounded morphology in both cells and a re-organization of F-actin, reducing the migration and invasive capacity significantly, and impaired the ability to organize the pseudovascular networks. In order to better understand the intracellular mechanisms elicited by AQP-1, we have investigated the role of LIN7, a PDZ protein which is involved in the recruitment and plasma membrane localization of interacting transporters, receptors, and adhesion molecules, linking them, through beta-catenin, to the cytoskeleton. Our results showed for the first time that AQP-1 co-immunoprecipitated with LIN7, and that the knock down of AQP-1 decreased the level of expression of LIN7 and beta-catenin. Interestingly, the inhibition of proteasome contrasted partially such a decrease. All together, our findings show, for the first time, that AQP-1 triggers an intracellular mechanisms modulating and stabilizing the organization of cytoskeleton, through LIN-7/beta-catenin interaction. Hear, we presented a model of the intracellular mechanism trigger by AQP-1 to regulate these process. Finally, we attempt to speculate that the skeleton-linked AQP-1, feel the degree of membrane skeleton distension and can regulate the state of cell volume necessary for polarization, migration and tube formation.