Actin depolymerisation and crosslinking join forces with myosin II to contract actin coats on fused secretory vesicles

Abstract

In many secretory cells actin and myosin are specifically recruited to the surface of secretory granules following their fusion with the plasma membrane. Actomyosin-dependent compression of fused granules is essential to promote active extrusion of cargo. Yet, little is known about molecular mechanisms regulating actin coat formation and contraction. Here we provide a detailed kinetic analysis of the molecules regulating actin coat contraction on fused lamellar bodies (LBs) in primary alveolar type II cells. We demonstrate that Rock1 and myosin light chain kinase (MLCK) translocate to fused LBs and activate myosin II on actin coats. Yet, myosin II activity is not sufficient for efficient actin coat contraction. In addition, cofilin-1 and α-actinin translocate to actin coats. Rock1-dependent, regulated actin depolymerisation by cofilin-1 in cooperation with actin crosslinking by α-actinin is essential for complete coat contraction. In summary, our data suggest a complementary role for regulated actin depolymerisation/crosslinking and myosin II activity to contract actin coats and drive secretion.