Unconventional myosin-Va (MYO5A) (MYO5A)

Unconventional myosin-V is a class of actin-based motor proteins that play a vital role in the intracellular transport of organelles and vesicles. In humans, the family comprises three isoforms (Va, Vb, and Vc), with Myosin Va being the most extensively studied for its role in transporting melanosomes in skin cells and synaptic vesicles in the brain (1). Mutations in the MYO5A gene are the primary cause of Griscelli syndrome type 1, a rare autosomal recessive disorder characterized by pigmentary dilution and severe neurological impairment (2). Myosin Vb is critical for membrane recycling in epithelial cells, and its dysfunction leads to microvillus inclusion disease, a life-threatening diarrheal condition (3). From a therapeutic perspective, Myosin V is an emerging target in oncology, as it facilitates the transport of vesicles containing pro-migratory factors that drive cancer cell invasion and metastasis (4). While small molecule inhibitors like pentachloropseudilin are used in research to probe its ATPase cycle, there are currently no FDA-approved drugs specifically targeting Myosin V, though it remains a significant focus for treating pigmentary and neurodegenerative conditions (5). Citations: (1) UniProt Consortium. "Unconventional myosin-Va (P42108)." UniProtKB. (2) Pastural, E., et al. (1997). "Griscelli disease maps to chromosome 15q21 and is associated with mutations in the myosin-Va gene." Nature Genetics. (3) Müller, T., et al. (2008). "MYO5B mutations cause microvillus inclusion disease and disrupt epithelial cell polarity." Nature Genetics. (4) Fedoryshchak, R. O., et al. (2020). "Small molecule inhibitors of unconventional myosins." ACS Chemical Biology. (5) Hammer, J. A., & Sellers, J. R. (2012). "Walking to work: roles for class V myosins as cargo transporters." Nature Reviews Molecular Cell Biology.

Other names

Myosin-VaMyosin VDilute myosin heavy chain non-muscleMyosin heavy chain 12MYH12MYO5Unconventional myosin-VMyosin VbMyosin Vc

Small molecule inhibitors typically target the ATPase activity of the motor domain or interfere with the actin-binding cycle, thereby preventing the translocation of cargo along actin filaments.