Dynein is a family of motor proteins operating within cells. These molecular machines convert chemical energy into mechanical work, enabling various forms of movement and transport at a microscopic scale. Dynein’s ability to move along cellular tracks, known as microtubules, enables its diverse functions. This protein family plays a role in maintaining cellular organization.
The Molecular Machinery of Dynein
Dyneins exist as large protein complexes, typically weighing between 0.7 and 1.8 megadaltons (MDa), with force generation occurring in heavy chains. Each heavy chain, a substantial protein of about 500 kDa, contains a motor domain that consumes ATP to produce movement. This motor domain includes a ring of six AAA+ (ATPases associated with diverse cellular activities) domains, from which several extensions emerge.
One extension, the stalk, contains the microtubule-binding domain, which interacts with microtubules. Another extension, the linker, connects the AAA+ ring to the cargo-binding end of the motor and undergoes movements during the ATP hydrolysis cycle to generate force. When ATP binds to a site on the dynein motor, the microtubule-binding domain releases its grip, and the linker bends. After ATP hydrolysis, the microtubule-binding domain rebinds, causing the linker to straighten and produce a “power stroke” that displaces the cargo.
Dyneins are categorized into two types: cytoplasmic dyneins and axonemal dyneins. Cytoplasmic dynein is found in all animal cells and some plant cells, involved in intracellular transport and cell division. Axonemal dynein is located in cells possessing cilia and flagella, where it facilitates their beating motion. While cytoplasmic dynein can move continuously along microtubules without detaching, axonemal dynein performs a non-processive, sliding motion between microtubules.
Dynein’s Diverse Roles in the Cell
Dynein plays diverse roles within the cell, particularly in transporting various components toward the cell’s center, a process known as retrograde transport. Cytoplasmic dynein moves membrane-bound vesicles and organelles like lysosomes, endosomes, and mitochondria, to their destinations. This transport maintains cellular organization and delivers necessary molecules throughout the cell.
Dynein also holds importance in cell division, contributing to both mitosis and meiosis. During these processes, dynein helps in positioning the mitotic spindle, a structure that organizes chromosomes for segregation. It also assists in the alignment and movement of chromosomes during metaphase and anaphase. Dynein contributes to the assembly and integrity of the mitotic spindle.
Beyond intracellular transport and cell division, axonemal dynein is responsible for the movement of cilia and flagella. These hair-like structures extend from the cell surface and are involved in diverse functions, such as propelling sperm cells and clearing mucus from airways. Axonemal dynein motors are arranged on microtubules within the cilium or flagellum, generating a sliding motion between adjacent microtubules. This coordinated sliding results in the bending or beating patterns of these cellular appendages.
When Dynein Goes Wrong: Implications for Health
Dysfunction or mutations in dynein can lead to health conditions. One example is Primary Ciliary Dyskinesia (PCD), a genetic disorder characterized by impaired cilia function. In PCD, defects in axonemal dynein prevent cilia from beating. This leads to chronic respiratory problems due to inefficient mucus clearance and can also cause infertility in males due to immotile sperm.
Impaired dynein-mediated transport is also linked to neurological disorders. For example, mutations in the cytoplasmic dynein heavy chain gene have been identified as a cause of Charcot-Marie-Tooth disease (CMT). This inherited condition affects peripheral nerves, leading to progressive muscle weakness and sensory loss. The disruption of dynein’s role in transporting cellular components along neuronal axons contributes to the degeneration of nerve fibers.
Dynein’s role in cell division and nuclear migration can also contribute to developmental issues. Abnormalities in cytoplasmic dynein or its regulatory proteins can cause malformations of cortical development, such as lissencephaly, pachygyria, and polymicrogyria. These conditions involve abnormal brain development, highlighting the impact of dynein’s functioning on tissue and organ development.