Arf6 determines tissue architecture by stabilizing intercellular adhesion

Correct cell shape is indispensable for tissue architecture, with cell shape being determined by cortical actin and surface adhesion. The role of adhesion in remodeling tissue is to counteract the deformation of cells by force, resulting from actomyosin contractility, and to maintain tissue integrity. The dynamics of this adhesion is critical to the processes of cell shape formation and maintenance. Here, we show that the trafficking molecule, Arf6, has a direct impact on cell elongation, by acting to stabilize E-cadherin-based adhesion complexes at the cell surface, in addition to its canonical role in endocytosis. We demonstrate that these functions of Arf6 are dependent on the molecule Flotillin1, which recruits Arf6 to the plasma membrane. Our data suggest that Arf6 and Flotillin1 operate in a pathway distinct from clathrin-mediated endocytosis. Altogether, we demonstrate that Arf6- and Flotillin1-dependent regulation of the dynamics of cell adhesion contributes to molding tissue in vivo.