myosinVa

Myosin Va is an actin-based molecular motor in the class V myosins. It functions as a dimeric, processive motor that moves along actin filaments toward the plus (barbed) end, transporting diverse cargo such as organelles and vesicles within the cytoplasm. The motor uses ATP hydrolysis to generate movement through conformational changes in its lever arm.

Structure and mechanism: Each heavy chain contains an N-terminal motor domain, a long coiled-coil region for dimerization, and a C-terminal globular tail that binds cargo. The lever arm is formed by six IQ motifs that bind light chains in the form of calmodulin-family proteins, creating a flexible, elongated motor. The tail mediates cargo binding via adaptor proteins, enabling specific cargo recognition. Myosin Va is regulated by autoinhibition in the absence of cargo and becomes activated upon cargo binding.

Function and cargo: Myosin Va transports a variety of cargoes, including secretory granules, late endosomes, mitochondria, and pigment-containing melanosomes. In melanocytes, it interacts with the Rab27a–melanophilin complex to position melanosomes along actin filaments for peripheral distribution, a process essential for pigmentation. In neurons and other cell types, it contributes to synaptic vesicle trafficking and organelle positioning, supporting localized delivery of membrane and protein cargo.

Clinical relevance: Mutations in MYO5A, the gene encoding myosin Va, cause Griscelli syndrome type 1, a disorder featuring hypopigmentation, immunological problems, and neurological symptoms, reflecting the motor’s role in pigment and organelle transport. Myosin Va shares functional parallels with other myosin V isoforms (Vb, Vc) that have distinct tissue distributions and cargo preferences.