Flotillin-2 regulates the dynamics of focal adhesions by interacting with alpha-actinin and influencing FAK phosphorylation

Cell migration is a multistep process comprising the formation of protrusions, generation of cell-matrix-adhesions, translocation of the cell body, release of adhesions and, retraction of the cell rear.

The family of flotillin proteins contains two well-conserved, ubiquitously expressed members, flotillin-1 and flotillin-2. Flotillins are associated with detergent-resistant membranes or membrane rafts by means of acylation. They show a strong tendency to form both homo- and heterooligomers, which regulate their cellular localization and function. Flotillins have been associated with several signal transduction pathways.

We have previously shown that flotillin-2/ is important for cell matrix adhesion during cell spreading [1].

In this study, we aimed at characterizing the molecular mechanism of flotillin function in cell-matrix adhesion and the role of individual flotillins in the regulation of focal adhesions.

We here show that flotillins are important for cell migration and morphology of focal adhesions. Depletion of flotillin-2, but not of flotillin-1, affects the autophosphorylation of FAK on Tyr397, indicating a role in the regulation of FA dynamics, whereas both flotillins are required for proper Erk phosphorylation. α-actinin was identified as a direct interaction partner of flotillins, which may provide a molecular link between flotillins, FAK and the regulation of FA dynamics.