Myosin IIA is a molecular motor protein in the body’s non-muscle cells that generates force for various cellular activities. It functions by pulling on the cell’s internal framework of actin filaments to create tension and facilitate movement. This action allows cells to change shape, move, and divide.
The Structure of Myosin IIA
A functional Myosin IIA molecule is a hexamer, composed of six protein chains: two heavy chains, two essential light chains, and two regulatory light chains. The proper assembly of these parts is required for the protein’s activity.
The two heavy chains form the molecule’s core and provide its motor capabilities. Each heavy chain has a large, globular “head” region that binds to actin filaments and uses energy from ATP hydrolysis to generate force. Extending from the head is a long tail that intertwines with the other heavy chain’s tail, forming a stable, coiled-coil structure.
The smaller light chains are situated at the junction between the head and tail of each heavy chain, an area called the neck or lever arm. The two essential light chains provide structural stability to this flexible neck region. The two regulatory light chains are primary sites for controlling the motor’s activity.
Individual Myosin IIA hexamers can self-assemble into larger structures called bipolar filaments. In this arrangement, molecules cluster with their tails interlocked at the center and their motor heads pointing in opposite directions. This organization allows the filament to pull on two different actin filaments, generating contractile force.
Key Functions in the Cell
The functions of Myosin IIA originate from its ability to generate pulling forces on the actin cytoskeleton. The cell uses this contractile capability for mechanical tasks like cell division and migration, which are necessary for survival and proliferation.
A primary role for Myosin IIA is in cytokinesis, the final step of cell division. After the genetic material is separated, the cell divides its cytoplasm to form two daughter cells. A structure called the contractile ring, composed of actin and Myosin IIA, assembles at the cell’s equator. This ring constricts like a purse string, pinching the parent cell in two.
Cell migration also depends on force generated by Myosin IIA. To move, a cell coordinates the extension of its leading edge with the retraction of its trailing end. Myosin IIA concentrates at the rear of the cell, creating the contractile force to pull the back of the cell forward, allowing it to crawl.
Myosin IIA also maintains a cell’s shape by generating tension within the actin cortex, a network of filaments beneath the cell membrane. This tension provides structural integrity and defines the cell’s form. The force is also transmitted across the cell membrane to strengthen adhesions with neighboring cells and the extracellular matrix.
How Myosin IIA Activity Is Controlled
The cell precisely controls Myosin IIA to ensure force is generated at the correct time and place. In its default state, the molecule exists in a folded, compact conformation where the tail domain folds back to interact with the head region. This locks the molecule in an “off” state, preventing it from assembling into active bipolar filaments and consuming ATP.
The primary “on” switch for Myosin IIA is phosphorylation. This process attaches a phosphate group to each of the two regulatory light chains, a task carried out by enzymes called kinases. The negative charge of the phosphate group causes a conformational change, forcing the molecule to unfold from its inhibited state into an extended, active shape.
Once unfolded, Myosin IIA assembles with other activated molecules to form bipolar filaments. The process is reversible, allowing the cell to turn the motor off. Enzymes called phosphatases remove the phosphate groups from the regulatory light chains, signaling the molecule to refold into its inactive state. This cycle allows the cell to manage its internal tension.
Connection to Human Disease
The instructions for building the Myosin IIA heavy chain are encoded in a gene called MYH9. Mutations in this gene can lead to a group of inherited conditions called MYH9-related disorders. These disorders are autosomal dominant, meaning inheriting just one defective copy of the gene is enough to cause the condition. The resulting faulty protein disrupts cellular functions in various tissues.
The defining symptom of MYH9-related disorders is macrothrombocytopenia, which involves abnormally large platelets and a reduced platelet count. This occurs because Myosin IIA is involved in platelet formation from precursor cells called megakaryocytes. The defective protein impairs their normal fragmentation, leading to the release of giant, dysfunctional platelets and subsequent bleeding tendencies.
Because Myosin IIA’s role in maintaining cell shape is widespread, its malfunction can affect other tissues beyond blood platelets. Patients with MYH9-related disorders often develop additional complications over time. These can include kidney problems (nephropathy), hearing loss, and cataracts, all stemming from the protein’s impaired function in those organs.