Kinesin motor proteins are molecular machines that function as tiny transporters, moving various cellular components along specific tracks. This movement is essential for the organization and proper functioning of all living cells.
How Kinesins Operate
A kinesin motor protein has a structure that allows it to perform transport. It consists of two globular “heads” or motor domains, which act like feet, connected to a long stalk and a tail domain. The two heads bind to cellular roadways called microtubules, which are long, hollow cylinders made of protein. The tail region attaches to the cargo, such as vesicles, organelles, or other molecules.
Kinesin movement along a microtubule is a “walking” motion. This process is fueled by the hydrolysis of adenosine triphosphate (ATP), the cell’s primary energy currency. Each step involves one kinesin head binding to ATP, causing a conformational change that propels the other head forward to the next binding site on the microtubule. This hand-over-hand mechanism allows kinesin to move unidirectionally along the microtubule track, towards the “plus end” of the microtubule, which is away from the cell’s center and towards its periphery.
Essential Cellular Roles
Kinesins are diverse, with a superfamily comprising at least 45 different genes in humans, each contributing to various cellular processes. Their most recognized function is intracellular transport. Kinesins carry various “cargo,” including vesicles, mitochondria, and other organelles, ensuring these components reach their precise destinations within the cell. This directed movement is important in large cells, such as neurons, where materials synthesized in the cell body must be transported long distances down axons to their terminals.
Beyond general transport, kinesins play a specialized role in cell division, during mitosis and meiosis. They are involved in forming the mitotic spindle, a complex structure of microtubules that helps separate chromosomes. Kinesin-5 family proteins, for instance, slide microtubules apart within the spindle, contributing to its elongation. Kinesin-13 family members help depolymerize microtubules, ensuring accurate chromosome segregation into daughter cells. This precise coordination of movement maintains the correct number of chromosomes in newly formed cells.
Kinesins and Human Health
Dysfunction of kinesin motor proteins can impact human health. When these transporters do not operate correctly, the precise delivery of cellular cargo is disrupted, leading to disease. This is evident in neurological disorders, where impaired transport along the long axons of nerve cells can be damaging.
For example, defects in kinesin-mediated axonal transport are associated with neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. In Alzheimer’s disease, tau and beta-amyloid proteins can inhibit certain kinesins, leading to impaired transport of proteins, lipids, and mitochondria within neurons. Specific kinesin defects, like those in KIF1C, are also linked to hereditary spastic paraplegia, a condition affecting motor neurons.
Kinesins also have implications in cancer. Given their role in cell division, particularly in forming the mitotic spindle and segregating chromosomes, errors in kinesin function can contribute to uncontrolled cell growth and tumor formation. Some kinesins are overexpressed in cancers, and researchers are exploring kinesin inhibitors as therapeutic targets to arrest cell division in cancer cells. For instance, inhibitors targeting KIF11 (also known as Eg5) are under evaluation for treating several cancers, including prostate, breast, and renal cancer, by disrupting spindle assembly and inducing cell death.