Myosin V (MyoV) belongs to the large superfamily of motor proteins found in eukaryotic cells. These molecular machines convert the chemical energy stored in adenosine triphosphate (ATP) into physical movement. Myosin V specifically interacts with and travels along the actin cytoskeleton, one of the cell’s primary internal track systems.
Defining the Myosin V Motor
The Myosin V protein functions as a dimer, composed of two identical heavy chains, each featuring a motor domain, a neck region, and a tail section. Unlike muscle myosin (Myosin II), which takes a single stroke and detaches, Myosin V is highly processive, allowing it to take many consecutive steps without falling off its track. This processivity is achieved because at least one of the two heads remains firmly attached to the actin filament throughout the movement cycle.
The protein moves using a coordinated “hand-over-hand” walking motion, similar to how a person walks by alternately moving their feet. This mechanism is facilitated by an unusually long neck region, often called a lever arm, which dictates the length of each step. Myosin V takes large, uniform steps of approximately 36 nanometers, which corresponds precisely to the helical repeat distance of the actin filament.
Key Biological Roles in Cellular Transport
Myosin V acts as a primary delivery system, hauling numerous types of intracellular cargo toward the cell periphery, which is the barbed end of the actin filaments. This function is accomplished by the protein’s tail domain, which connects to the cargo via specific adaptor proteins. The cargoes Myosin V transports include large organelles, vesicles, and complexes of messenger RNA (mRNA).
One fundamental role is the movement and proper positioning of organelles, such as mitochondria, the endoplasmic reticulum, and vacuoles. In many cells, Myosin V works in conjunction with microtubule-based motors, like kinesin, to ensure cargo reaches its destination. Kinesin often handles the long-range transport along microtubules deep within the cell, while Myosin V takes over for the short-range, final delivery stage across the actin-rich cortex near the cell membrane.
Myosin V’s function is particularly important in nerve cells, where it contributes to synaptic plasticity and the guidance of growth cones, the exploratory tips of developing or regenerating nerve cells. In the Purkinje cells of the cerebellum, Myosin V helps transport materials necessary for communication between neurons, including the movement of smooth endoplasmic reticulum into the dendritic spines. Defects in this neuronal transport can impair motor learning and coordination.
A well-studied example of its transport function occurs in melanocytes, the pigment-producing cells in the skin and hair. Here, Myosin V is responsible for moving melanosomes—vesicles containing the pigment melanin—out to the tips of the cell extensions. This movement is necessary for the subsequent transfer of pigment to surrounding skin and hair cells, and the inability to properly transport melanosomes results in the visible loss of pigmentation.
Myosin V and Human Disease
The most recognized human disorder linked directly to a defective Myosin V is Griscelli syndrome type 1 (GS1). This rare autosomal recessive disorder is caused by mutations in the MYO5A gene that encodes the Myosin V protein.
Patients with GS1 exhibit a characteristic partial albinism, known as pigmentary dilution, which manifests as silvery-gray hair and abnormally light skin. This is a direct result of the failure of Myosin V to transport melanosomes from the center of the melanocyte to the periphery. The pigment granules accumulate near the cell nucleus instead of being distributed, leading to visual hypopigmentation.
Griscelli syndrome type 1 is also associated with neurological dysfunction, linked to the protein’s failure in neuronal transport. Mutations in MYO5A can lead to severe neurological symptoms, including ataxia (lack of voluntary coordination of muscle movements) and clonic convulsions. The failure to correctly position organelles and vesicles in nerve cells compromises synaptic signaling and the maintenance of neuronal structure.