What is Myosin 5 and What Does It Do?

Myosin 5 is a motor protein that functions as a microscopic transporter within the cell. It belongs to a large family of proteins known as myosins, which convert chemical energy into mechanical force to move along cellular tracks. This particular class of myosin is not involved in large-scale muscle contraction but specializes in moving a variety of internal components. This intracellular transport system is necessary for maintaining cellular organization, allowing cells to perform specialized functions and respond to their environment.

The Blueprint of Myosin 5: A Molecular Machine

The Myosin 5 protein is a dimeric molecule, composed of two identical heavy chains that intertwine to form a functional unit. Its structure is divided into three distinct domains. The first is the N-terminal motor domain, or head, which is the engine of the molecule. This structure binds to cellular filaments made of actin and breaks down adenosine triphosphate (ATP) to release energy for movement.

Following the motor domain is a long, rigid neck region that acts as a lever arm. This section has binding sites for smaller proteins called calmodulin, and the number of these proteins bound to the neck influences the lever arm’s stiffness and the motor’s step size. The opposite end of the protein is the C-terminal tail domain, a region responsible for recognizing and binding to specific cellular cargo. This part of the molecule is highly specialized, allowing different types of Myosin 5 to transport different materials.

How Myosin 5 Walks: Powering Cellular Transport

Unlike some motor proteins that take a single step and detach, Myosin 5 is a processive motor. This means it can take many successive steps along an actin track without letting go, a feature enabled by its two-headed structure. This processivity allows for the long-distance transport of cargo across the cell.

This walking motion is powered by the cyclical binding and hydrolysis of ATP in the motor domains. When a motor head binds an ATP molecule, its affinity for the actin filament is reduced, causing it to detach. The ATP is then hydrolyzed into ADP and inorganic phosphate (Pi), which triggers a conformational change that “cocks” the head forward. The head then rebinds to a new site further along the actin filament and the release of Pi initiates the “power stroke,” a forceful movement that pulls the cargo forward.

The two heads work in a coordinated “hand-over-hand” mechanism. While one head is detached and moving forward, the other remains firmly bound to the actin filament, preventing the complex from floating away. This coordinated action allows the protein to “walk” with a large step size.

Myosin 5’s Special Deliveries: Cargo and Connections

Myosin 5 is a versatile delivery vehicle, responsible for transporting a wide array of materials. Its cargo includes large organelles like melanosomes (the pigment granules that determine skin color) and portions of the endoplasmic reticulum, a network involved in protein and lipid synthesis. It also transports smaller packages called vesicles, such as secretory vesicles that release substances from the cell, and synaptic vesicles that hold neurotransmitters.

The specificity of what Myosin 5 carries is determined by its tail domain. This region often connects to cargo through a system of adaptor proteins, creating a molecular link between the motor and its payload. A well-studied example involves the transport of melanosomes, where Myosin 5a connects to the melanosome via an adaptor protein named melanophilin, which in turn binds to a Rab27a protein on the melanosome’s surface.

This interaction with Rab proteins is a common theme. Rab proteins reside on the surface of organelles and vesicles, acting like postal codes that identify the organelle. By recognizing specific Rab proteins, different Myosin 5 isoforms can engage with the correct cargo.

Myosin 5 at Work: Vital Roles in Cell Function

The transport activities of Myosin 5 are integral to a diverse range of cellular processes. In melanocytes, Myosin 5a is responsible for distributing melanosomes throughout the cell’s periphery. This distribution is what gives skin and hair its even pigmentation. Without this transport, the pigment would remain clustered around the cell’s nucleus, leading to a loss of coloration.

In the nervous system, Myosin 5 moves synaptic vesicles to the tips of nerve cell axons. This ensures a ready supply of neurotransmitters is available for release, facilitating communication between neurons. The motor protein also helps to anchor and position the endoplasmic reticulum, ensuring this organelle is properly distributed to carry out its functions.

The consequences of its malfunction highlight its importance. Mutations in the gene that codes for Myosin 5a can lead to a rare genetic disorder in humans called Griscelli syndrome. This condition is characterized by partial albinism due to the failure of melanosome transport, as well as neurological and immunological problems from defects in vesicle transport.