The internal world of a cell is maintained by the cytoskeleton, a dynamic network of protein filaments. Microtubules, the largest components of this network, serve as long, rigid tracks spanning the entire cell. Specialized motor proteins travel these tracks, facilitating the transport of materials and generating cellular movement. Dynein is one such molecular motor protein, and its partnership with microtubules is fundamental to the survival and function of nearly all eukaryotic cells.
Defining the Cellular Infrastructure
Microtubules are hollow, cylindrical polymers built from repeating tubulin units. These units are alpha-tubulin and beta-tubulin heterodimers, which link end-to-end to form long strands called protofilaments. Typically, thirteen protofilaments align side-by-side to form the microtubule wall, creating a hollow tube approximately 25 nanometers in diameter.
This arrangement gives the microtubule structural polarity. One end, known as the plus end, is generally oriented toward the cell periphery and grows more rapidly. The opposite minus end is typically anchored near the cell’s center in a structure called the microtubule-organizing center.
Dynein is a large, multi-subunit protein complex that interacts directly with these tracks. The core is the heavy chain, which includes a globular head domain responsible for generating force and a stalk that binds to the microtubule. An N-terminal tail domain recruits accessory subunits that facilitate cargo attachment.
Dynein is classified into two major categories based on its function. Cytoplasmic dynein is found throughout the cell’s interior and primarily moves cellular components. Axonemal dynein is restricted to specialized, motile structures like cilia and flagella, where it is fixed in place to generate a bending motion.
The Mechanism of Dynein’s Movement
Dynein’s movement along a microtubule is a precise sequence of events driven by chemical energy from adenosine triphosphate (ATP). Dynein belongs to the AAA+ family of ATPases, meaning its globular motor domain contains six repeating domains. The first domain, AAA1, acts as the primary site for converting chemical energy into mechanical force.
The cycle begins with the dynein motor domain bound to the microtubule via its stalk. When an ATP molecule binds to the AAA1 site, it causes a conformational shift in the motor domain. This ATP binding event, followed by its hydrolysis into ADP and inorganic phosphate, generates a large-scale swing in the internal linker domain.
This swing acts as a priming stroke, preparing the motor for its next step and moving the entire dynein complex forward along the microtubule. The motor domain then releases the inorganic phosphate, which triggers the power stroke—a forceful return of the linker domain to its resting state, effectively pulling the trailing head forward.
Dynein motors are exclusively retrograde motors. The mechanochemical cycle, powered by the sequential binding and hydrolysis of ATP, is engineered to move the motor only toward the microtubule’s minus end. This is the opposite direction of the other primary microtubule motor, kinesin, which generally moves toward the plus end, enabling a bidirectional flow of materials within the cell.
Dynein’s Role in Intracellular Cargo Transport
The primary function of cytoplasmic dynein is pulling various cellular components from the cell’s periphery back toward the center. This retrograde transport is essential for clearing used materials and positioning organelles near the nucleus. The list of items transported by dynein is diverse, including membranous structures like endosomes, lysosomes, and vesicles produced by the endoplasmic reticulum, as well as entire organelles like mitochondria.
Dynein rarely attaches directly to its cargo. Instead, it relies on dynactin, a large multi-protein complex that acts as a linker. Dynactin, along with coiled-coil “activating adaptors,” forms a tripartite complex with dynein. These adaptors, such as BICD2 and Hook proteins, physically link the dynein-dynactin machinery to the specific surface of a particular cargo.
The formation of this adaptor-dynactin-dynein complex is necessary to switch the dynein motor from an autoinhibited, low-activity state to a highly processive, walking state. This activation is particularly important in large cells, such as neurons, which can have axons up to a meter long. Dynein-driven retrograde axonal transport moves materials, including signaling molecules and old organelles, from the axon terminals back to the cell body for degradation or recycling.
This transport can occur at average speeds of up to 2 micrometers per second. The same dynein machinery is also exploited by certain pathogens, such as the rabies and herpes simplex viruses. They hijack the retrograde transport system to travel from the nerve terminal back to the cell body, where they can replicate.
Dynein’s Role in Generating Cell Movement
While cytoplasmic dynein moves cargo, axonemal dynein generates large-scale motion by powering the beating of cilia and flagella. These organelles are structurally defined by an internal arrangement of microtubules known as the axoneme. The axoneme typically consists of nine outer doublet microtubules surrounding a central pair, often called the “9+2” arrangement.
Axonemal dynein motors are permanently fixed to the side of one outer doublet microtubule, and their tail is tethered to the adjacent doublet microtubule. When the dynein motor hydrolyzes ATP, it attempts to walk along the neighboring microtubule. Because the tail is fixed, this action is converted into a sliding force.
This dynein-driven microtubule sliding is the core mechanism of ciliary and flagellar movement. Since the microtubules within the axoneme are cross-linked, the sliding is constrained and cannot continue indefinitely. This resistance converts the linear sliding force into a localized bending motion of the entire structure.
The rhythmic, coordinated beating motion requires precise regulation of the dynein motors. Dynein arms on one side of the axoneme are activated while those on the opposite side are temporarily inactivated. This creates the asymmetric forces needed to produce the characteristic waveform. This orchestrated activity allows cilia to move fluid over a cell surface, such as mucus in the respiratory tract, or enables flagella to propel an entire cell, as seen in sperm.