How Do Dynein and Microtubules Work Together?

Within a cell, a partnership exists between microtubules and motor proteins called dyneins, which work together to manage cellular structure and movement. Microtubules provide a network of tracks, and dynein acts as a motor that travels along them to transport cargo and generate force. This collaboration drives processes ranging from the transport of materials to the mechanics of cell division.

The Structure and Dynamics of Microtubules

Microtubules are a primary component of the cytoskeleton, the internal scaffolding that gives a cell its shape. These structures are hollow tubes constructed from repeating protein subunits called alpha-tubulin and beta-tubulin. The tubulin dimers polymerize to form long filaments called protofilaments, and around 13 of these align to create the hollow microtubule. This architecture provides structural support throughout the cell’s cytoplasm.

A defining characteristic of microtubules is their polarity, meaning the two ends are distinct. One end, the “plus” end, is where growth occurs most rapidly. The opposite end is the “minus” end, which is anchored in a microtubule-organizing center (MTOC). This structural polarity is a direct result of the orientation of the tubulin dimers within the protofilaments.

This polarity underpins a behavior known as dynamic instability, which is the constant switching between phases of growth (polymerization) and shrinkage (depolymerization). This allows the microtubule network to be highly adaptable, rapidly reorganizing itself to meet the changing needs of the cell. This dynamic nature enables microtubules to explore the cellular space and exert forces.

Dynein: The Molecular Motor

Dynein is a family of motor proteins that converts chemical energy into mechanical work, enabling movement along microtubules. A dynein molecule is composed of several protein chains, including two identical heavy chains that form the motor’s core. These heavy chains contain large, globular head domains with sites for binding to microtubules and hydrolyzing adenosine triphosphate (ATP).

Extending from the motor domains is a tail region responsible for attaching to cellular cargo. The tail interacts with smaller proteins, known as intermediate and light chains, which link dynein to the specific materials it transports. This modular design allows different dynein molecules to be specialized for carrying different loads.

There are two main classes of dynein, distinguished by their location and function. Cytoplasmic dynein operates in the cytoplasm and is involved in intracellular transport and organization. The other class, axonemal dynein, is found exclusively in cilia and flagella, where it powers their movement.

How Dynein Moves Along Microtubules

The movement of dynein along a microtubule is a coordinated process described as “walking.” Dynein motors travel toward the minus end of the microtubule, a direction known as retrograde transport. This directed movement allows dynein to carry cargo from the cell periphery toward the cell center. For many dyneins, this movement is processive, meaning the motor can take many steps without detaching.

The energy for this movement is derived from the hydrolysis of ATP. The process begins when a dynein head binds an ATP molecule, which triggers a conformational change causing it to release from the microtubule. After ATP hydrolysis, the head swings forward and the microtubule-binding domain reattaches to a new site further along the track.

The release of the phosphate group and then ADP causes the dynein head to execute a “power stroke,” a conformational change in the protein that pulls the attached cargo. The two heads of the dynein motor work in a coordinated, hand-over-hand fashion. This ensures that one head is always attached to the microtubule while the other is stepping forward.

Essential Cellular Functions Driven by Dynein and Microtubules

One of the primary functions of this partnership is intracellular transport. Dynein motors attach to various cargoes, such as vesicles, lysosomes, and parts of the Golgi apparatus, and transport them along the microtubule network. This directed delivery system ensures that cellular components reach their correct destinations to maintain organization.

During cell division, or mitosis, the dynein-microtubule system organizes microtubules into the bipolar mitotic spindle, the apparatus that segregates chromosomes. Dynein pulls on microtubules from various locations, including the cell cortex and chromosomes, to focus the spindle poles and align the chromosomes. The force generated by dynein also positions the entire spindle within the dividing cell, which is a factor in asymmetric cell divisions.

In cells with cilia and flagella, axonemal dynein drives their movement. These structures are built from a precise arrangement of microtubules called an axoneme. Axonemal dynein arms are attached to one microtubule while their motor heads bind and pull on an adjacent microtubule. This action causes the microtubules to slide past one another, and since they are anchored, this sliding is converted into a bending motion.

Consequences of Dynein-Microtubule System Failures

When the dynein-microtubule system malfunctions, the consequences for the cell and organism can be severe. Defects, often arising from genetic mutations in dynein or tubulin, disrupt cellular activities and lead to a range of human diseases. The specific symptoms depend on which cells are most affected by the faulty mechanisms.

In the nervous system, where long-distance transport along axons is constant, dynein defects can lead to neurodegenerative diseases. For example, some forms of lissencephaly, a brain development disorder, are caused by errors in neuronal migration. This process relies on dynein, and disruptions in axonal transport have also been linked to conditions like Charcot-Marie-Tooth disease.

Failures in axonemal dynein lead to a condition known as Primary Ciliary Dyskinesia (PCD). In individuals with PCD, cilia in the respiratory tract cannot beat effectively, preventing mucus clearance and leading to chronic respiratory infections. The immotility of sperm flagella also results in male infertility. Problems during cell division, such as improper chromosome segregation from dynein dysfunction, can result in cell death or contribute to genetic instability in some cancers.