Does the Actin Network Architecture Leverage Myosin-I Functions?

SIMPLE SUMMARY: Here, we review the known characteristics and functions of proteins called myosin-I. These mechanoenzymes belong to an ancient family of actin-dependent motors, found throughout eukaryotic cells, which are characterized by intracellular membrane-bound compartments. We elaborate on the surprising fact that many different functions have been attributed to these proteins, and highlight that we now need to understand how their enzymatic activity supports these functions. We propose to focus on the remodeling of the actin cytoskeleton, a higher-order dynamic scaffold typical for eukaryotic cells. ABSTRACT: The actin cytoskeleton plays crucial roles in cell morphogenesis and functions. The main partners of cortical actin are molecular motors of the myosin superfamily. Although our understanding of myosin functions is heavily based on myosin-II and its ability to dimerize, the largest and most ancient class is represented by myosin-I. Class 1 myosins are monomeric, actin-based motors that regulate a wide spectrum of functions, and whose dysregulation mediates multiple human diseases. We highlight the current challenges in identifying the “pantograph” for myosin-I motors: we need to reveal how conformational changes of myosin-I motors lead to diverse cellular as well as multicellular phenotypes. We review several mechanisms for scaling, and focus on the (re-) emerging function of class 1 myosins to remodel the actin network architecture, a higher-order dynamic scaffold that has potential to leverage molecular myosin-I functions. Undoubtfully, understanding the molecular functions of myosin-I motors will reveal unexpected stories about its big partner, the dynamic actin cytoskeleton.