Abstract
Unconventional myosins are multi-potent molecular motors that are assigned important roles in fundamental cellular processes. Depending on their mechano-enzymatic properties and structural features, myosins fulfil their roles by acting as cargo transporters along the actin cytoskeleton, molecular anchors or tension sensors. In order to perform such a wide range of roles and modes of action, myosins need to be under tight regulation in time and space. This is achieved at multiple levels through diverse regulatory mechanisms: the alternative splicing of various isoforms, the interaction with their binding partners, their phosphorylation, their applied load and the composition of their local environment, such as ions and lipids. This review summarizes our current knowledge of how unconventional myosins are regulated, how these regulatory mechanisms can adapt to the specific features of a myosin and how they can converge with each other in order to ensure the required tight control of their function.
Highlights
Myosins are molecular engines that utilise the energy released from ATP hydrolysis to produce mechanical work along the actin cytoskeleton
In vitro reconstitution experiments elegantly demonstrated that the mRNA cargo itself contributes to the stability of the complex, with the run length and frequency increasing with the number of motors recruited [149]
During the past two decades, biophysical, biochemical, structural and cellular observations have provided insights into the mechanistic details of how these modes of regulation are applied to specific classes of myosins (Table 1)
Summary
Myosins are molecular engines that utilise the energy released from ATP hydrolysis to produce mechanical work along the actin cytoskeleton. Various mechanisms have evolved in order to ensure that the right myosin is activated at the right time; that it adopts the appropriate conformation for its function; and that it interacts with the suitable binding partner in order to associate with the appropriate cargo and to be recruited at the correct intracellular location To this end, the regulation of myosins occurs at multiple levels: from gene expression and post-translational modifications, to the dynamic manipulation of their local environment which includes divalent cations, lipids, binding partners and applied load (Figure 2). Intracellular localization and function: Alternative splicing within the CBD and phosphorylation (SI isoform)
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