Mechanochemical regulation of membrane tension by endocytic processes in adherent cells

Plasma membrane tension regulates many key cellular processes, and in turn cells regulate their membrane tension by finely tuned mechanisms. Some of these mechanisms involve the regulation of exo-endocytic trafficking. A number of endocytic processes operate simultaneously at the cell surface, however a specific dynamin and clathrin-independent endocytic pathway, the CLIC/GEEC (CG) pathway, is rapidly and specifically upregulated upon a sudden reduction of membrane tension, resulting in the resetting of resting membrane tension. Moreover, inhibition (activation) of the CG pathway results in lower (higher) membrane tension. Alteration in membrane tension in adherent cells by stretching or generating hypotonic shock does not directly modulate CG endocytosis by a physical restriction imposed on the process. Instead, there is a mechano-chemical response to the cellular microenvironment that effects this control. This involves the activation of integrin receptors on specific extracellular matrices; vinculin, a mechano-transducer, which is recruited to focal adhesions, plays a key role in negatively regulating CG endocytosis. In its absence, CG endocytosis is unregulated, leading to altered membrane tension. This behaves as a control circuit where fast feedback inhibition (via Vinculin activation) and slow activation (via CG endocytosis) provides for homeostatic regulation of membrane tension in adherent cells.