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.
|Titolo:||Knock down of AQP1 in HMEC-1 and WM115 cells changes the organization of the cytoskeleton|
|Relatore:||LA PORTA, CATERINA|
|Supervisori e coordinatori interni:||MANTOVANI, ALBERTO|
|Data di pubblicazione:||2009|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
|Citazione:||Knock down of AQP1 in HMEC-1 and WM115 cells changes the organization of the cytoskeleton ; coordinatore: A. Mantovani ; relatore: C.A.M. La Porta. - Milano : Università degli studi di Milano. DIPARTIMENTO DI SCIENZE BIOMOLECOLARI E BIOTECNOLOGIE, 2009. ((21. ciclo, Anno Accademico 2007/2008.|
|Appare nelle tipologie:||13 - Tesi di dottorato discussa entro ottobre 2010|