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Abstract
Myosin is a diverse superfamily of motor proteins responsible for actin-based motility and contractility in eukaryotic cells. Myosin-18 family, including myosin-18A and myosin-18B, belongs to an unconventional class of myosin, which lacks ATPase motor activity, and the investigations on their functions and molecular mechanisms in vertebrate development and diseases have just been initiated in recent years. Myosin-18A is ubiquitously expressed in mammalian cells, whereas myosin-18B shows strong enrichment in striated muscles. Myosin-18 family is important for cell motility, sarcomere formation, and mechanosensing, mostly by interacting with other cytoskeletal proteins and cellular apparatus. Myosin-18A participates in several intracellular transport processes, such as Golgi trafficking, and has multiple roles in focal adhesions, stress fibers, and lamellipodia formation. Myosin-18B, on the other hand, participates in actomyosin alignment and sarcomere assembly, thus relating to cell migration and muscle contractility. Mutations of either Myo18a or Myo18b cause cardiac developmental defects in mouse, emphasizing their crucial role in muscle development and cardiac diseases. In this review, we revisit the discovery history of myosin-18s and summarize the evolving understanding of the molecular functions of myosin-18A and myosin-18B, with an emphasis on their separate yet closely related functions in cell motility and contraction. Moreover, we discuss the diseases tightly associated with myosin-18s, especially cardiovascular defects and cancer, as well as highlight the unanswered questions and potential future research perspectives on myosin-18s.
Highlights
Myosins are a large superfamily of proteins that are responsible for providing motility of various components in the cells and motility of cells, tissues, and organs
Not all myosin motors possess the ATPase-driven motor activity, exemplified by the recently discovered myosin-18 family consisting of myosin-18A and myosin-18B
Two independent findings of MYO18B mutations linked in human myopathies further confirmed the conserved function of myosin-18B in striated muscle development (Alazami et al, 2015; Malfatti et al, 2015)
Summary
Myosins are a large superfamily of proteins that are responsible for providing motility of various components in the cells and motility of cells, tissues, and organs. MYO18A is located on chromosome 11 and encodes for three major splice isoforms, a long myosin18Aα, a short myosin-18Aβ, and myosin-18Aγ, which is expressed in striated muscle (Horsthemke et al, 2019; Figure 1). Later studies showed that both N-terminal and the motor domain of myosin-18A possess actin-binding activity (Guzik-Lendrum et al, 2013; Taft et al, 2013).
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