AQP1 Is Not Only a Water Channel: It Contributes to Cell Migration through Lin7/Beta-Catenin

Elena Monzani,Caterina A M La Porta,Carla Perego,Riccardo Bazzotti,Neil Hotchin

doi:10.1371/journal.pone.0006167

Abstract

BackgroundAQP1 belongs to aquaporins family, water-specific, membrane-channel proteins expressed in diverse tissues. Recent papers showed that during angiogenesis, AQP1 is expressed preferentially by microvessels, favoring angiogenesis via the increase of permeability In particular, in AQP1 null mice, endothelial cell migration is impaired without altering their proliferation or adhesion. Therefore, AQP1 has been proposed as a novel promoter of tumor angiogenesis.Methods/FindingsUsing targeted silencing of AQP1 gene expression, an impairment in the organization of F-actin and a reduced migration capacity was demonstrated in human endothelial and melanoma cell lines. Interestingly, we showed, for the first time, that AQP1 co-immunoprecipitated with Lin-7. Lin7-GFP experiments confirmed co-immunoprecipitation. In addition, the knock down of AQP1 decreased the level of expression of Lin-7 and β-catenin and the inhibition of proteasome contrasted partially such a decrease.Conclusions/SignificanceAll together, our findings show that AQP1 plays a role inside the cells through Lin-7/β-catenin interaction. Such a role of AQP1 is the same in human melanoma and endothelial cells, suggesting that AQP1 plays a global physiological role. A model is presented.

Highlights

Aquaporins are a family of water-specific, membrane-channel proteins expressed in diverse tissues
Cell culture Human melanoma WM115 cell line derived from a primary epithelioid tumor (ATCC CRL 1675) was cultured in the basal medium Eagle (BME) supplemented with 10% fetal calf serum, 2 mM L-glutamine, 1% non-essential amino acids, 2% BME vitamin solution, 100 U/ml penicillin, 100 mg/ml streptomycin and 0,25 mg/ml amphotericin B (Invitrogen, Milan, Italy) as previously described [21]
Since AQP1 was demonstrated to be involved in angiogenesis [8], we investigated the effect of this water channel on cell migration in WM115 and HMEC-1 cells

Summary

Introduction

Aquaporins are a family of water-specific, membrane-channel proteins expressed in diverse tissues. In AQP1 null mice, an impairment of endothelial cell migration, without altering their proliferation or adhesion, was shown [8]. In this connection, AQP1 has been proposed as a novel promoter of tumor angiogenesis [9]. AQP1 belongs to aquaporins family, water-specific, membrane-channel proteins expressed in diverse tissues. Recent papers showed that during angiogenesis, AQP1 is expressed preferentially by microvessels, favoring angiogenesis via the increase of permeability In particular, in AQP1 null mice, endothelial cell migration is impaired without altering their proliferation or adhesion. AQP1 has been proposed as a novel promoter of tumor angiogenesis

Methods

Results

Conclusion