Myosin motor proteins are involved in the final stages of the secretory pathways

Abstract

In eukaryotes, the final steps in both the regulated and constitutive secretory pathways can be divided into four distinct stages: (i) the 'approach' of secretory vesicles/granules to the PM (plasma membrane), (ii) the 'docking' of these vesicles/granules at the membrane itself, (iii) the 'priming' of the secretory vesicles/granules for the fusion process, and, finally, (iv) the 'fusion' of vesicular/granular membranes with the PM to permit content release from the cell. Recent work indicates that non-muscle myosin II and the unconventional myosin motor proteins in classes 1c/1e, Va and VI are specifically involved in these final stages of secretion. In the present review, we examine the roles of these myosins in these stages of the secretory pathway and the implications of their roles for an enhanced understanding of secretion in general.

Figure 1. Roles played by myosin motor proteins in the final stages of secretion

Secretory vesicles or granules (‘carriers’) in the final stages of constitutive or regulated exocytosis undergo four discrete stages: 1) approach; 2) docking; 3) priming and 4) fusion. Transfer of carriers through these four stages relies on the actions of many different myosin motor proteins, particularly nonmuscle myosin II and unconventional myosins in classes 1c, 1e, V, and VI. The approach of secretory carriers to the plasma membrane through the F-actin cytoskeleton relies on transport by myosins 1c, 1e, and Va, as well as F-actin reorganization by myosin II. The docking of these carriers to SNARE proteins at the plasma membrane relies on the actions of myosin Va, which binds directly to the SNARE proteins syntaxin 1A and VAMP2. Priming of carriers at the membrane for subsequent fusion relies on carrier membrane remodeling by myosin Va. Finally, the fusion of individual carriers with the membrane is modulated by interactions between myosin II, myosin VI, and possibly myosin 1c with the actin cytoskeleton that produce the force necessary to open or close the fusion pore formed between each carrier and the plasma membrane.