The molecular composition of JRAB/MICAL-L2 droplets controls site-specific actin bundle morphology to drive cell-cell adhesion

JRAB (also known as MICAL-L2), an effector protein for the small G proteins Rab8A and Rab13, interacts with actin filaments (F-actin), actinin-1, actinin-4 and filaminA, and plays an important role in the spatiotemporal actin cytoskeletal reorganization underlying cell migration and cell-cell adhesion. JRAB forms droplets that include Rab8A by liquid-liquid phase separation, leading to deformation of the endosomal membrane. In this study, we showed that JRAB functions in actin dynamics as a droplet, leading to the development of cell-cell adhesions. In vitro reconstitution assays revealed that JRAB droplets promoted the assembly of thick F-actin bundles, a process that was distinct from that observed with JRAB in its soluble form. Moreover, we identified Rab13 as a modulator of JRAB droplet function. JRAB droplets containing Rab13 inhibited the formation of F-actin bundles. The difference in mechanical properties among those droplets might be correlated with the ability of JRAB to regulate F-actin bundle morphology. Taken together, our findings provide new insight into a previously unrecognized mechanism through which droplets regulate actin dynamics by changing their components.