Dynein retrograde transport is a process that moves materials within a cell from its outer regions toward the center. This internal traffic system functions like a highly organized delivery service, ensuring cellular components reach their correct destinations. The process is necessary for the health and function of nearly every cell.
The Cellular Transportation System
Cellular transport relies on protein filaments called microtubules, which form an extensive network of tracks spanning the cell’s interior. These structures act as dynamic superhighways that can be assembled and disassembled to meet a cell’s needs. Traveling along these roads are molecular motors that carry cargo.
The motor protein responsible for inward-bound traffic is dynein, which functions like a microscopic truck hauling cellular materials. This directional travel brings materials from the distant edges of the cell back to its main processing centers.
This inward journey contrasts with anterograde transport, which moves materials from the cell center outward. This outward-bound traffic is managed by a different family of motor proteins called kinesins. Together, dynein and kinesin create a two-way transportation system that allows the cell to manage its internal logistics.
The Mechanism of Movement
The dynein motor’s movement is an energy-dependent process converting chemical energy into mechanical force. The fuel for this is adenosine triphosphate (ATP), the cell’s primary energy currency. Dynein binds to and hydrolyzes ATP, breaking the molecule apart to release energy that powers a change in the protein’s shape, causing it to move.
The motion is often described as a “walk” along the microtubule track. Dynein has two “legs,” or motor domains, that alternately bind to and detach from the microtubule in a step-like fashion. This cycle of binding, power stroke, and release propels the motor and its cargo steadily along the microtubule.
This walking mechanism allows dynein to move cargo over long distances without detaching from its track. Dynein motors can move at average speeds of about 2 micrometers per second. This rate allows for the transport of materials over 10 to 20 centimeters per day, a capability required in long cells like neurons.
Essential Functions of Retrograde Transport
In the nervous system, retrograde transport is necessary for the function of long cells like neurons. It carries survival signals from the axon terminal back to the cell body, informing the nucleus of the cell’s condition. This pathway also transports used proteins and organelles back to the cell body for recycling.
During cell division, or mitosis, dynein plays a role in the separation of chromosomes. It helps organize microtubules into the mitotic spindle. Dynein motors anchor the spindle poles and pull the duplicated chromosomes apart, ensuring each new daughter cell receives a complete set of genetic material.
Dynein is also involved in positioning organelles within the cell, such as maintaining the location of the Golgi apparatus near the cell center. Dynein also transports other cargoes, including endosomes, mitochondria, and messenger RNA (mRNA) molecules, to their proper locations.
Consequences of Transport Failure
When dynein retrograde transport is impaired, the consequences can be severe for cells with long axons, like motor neurons. A breakdown in this system contributes to neurodegenerative diseases like Amyotrophic Lateral Sclerosis (ALS), Huntington’s disease, and Charcot-Marie-Tooth disease. This failure prevents the delivery of survival signals and inhibits the clearance of toxic protein aggregates, which can lead to neuron death.
Mutations in the genes that code for dynein or its associated proteins have been linked to motor neuron diseases. For example, a mutation in the dynactin subunit p150Glued is identified in a familial form of slowly progressive motor neuron disease. These genetic defects compromise the motor complex’s function, reducing its ability to transport cargo and leading to neuron degeneration.
The dynein transport system is also exploited by pathogens. Viruses like herpes simplex, rabies, and adenovirus can hijack the dynein motor after entering a cell. They use it as a shuttle to travel along microtubules to the nucleus, where the virus can insert its genetic material and begin replication.