Kinesin

Kinesin

In addition to actin, the cytoskeleton includes other components, notably intermediate filaments and microtubules. Microtubules serve as tracks for two classes of motor proteins — namely, kinesins and dyneins. Kinesins moving along microtubules usually carry cargo such as organelles and vesicles from the center of a cell to its periphery. Dyneins are important in sliding microtubules relative to one other during the beating of cilia and flagella on the surfaces of some eukaryotic cells.

Cells need to be able to transport a variety of molecules, and even entire organelles, around a cell. Cells achieve this movement using molecular motors, which produce the force required for transport through the hydrolysis of ATP.The three major classes of biological motors are kinesins, myosins and dyneins, each of which plays vital roles in a huge variety of cellular processes. Molecular motors move their cargo along actin filaments (myosins) or microtubules (kinesins and dyneins), which act as highways within a cell for trafficking a wide variety of cargo.Kinesins (KIF proteins) are a family of molecular motors that contain a highly conserved ~340 residue motor domain that uses ATP hydrolysis to walk along a microtubule.

The functions of kinesin

The function roles of kinesin motors inside cells are wildly assumed to be related to organelle and molecular transport and movement and force generation in mitosis. The members of kinesin superfamily which are responsible for intracellular transport are kinesin-1, kinesin-2, kinesin-3, kinesin-4 and kinesin-6 whereas kinesin-4 and kinesin-6 also participate in mitosis. The other kinesin families, in contrast, all have function in mitosis. For example, members of Kinesin-1 family are responsible for transporting organelles and macromolecular complex, such as mitochondria, lysosomes, tubulin oligomers, mRNA complex while members in kinesin-2 family transport vesicles and macromolecules in axons of mammalian neurons and play important roles in the molecular assembly of cilia and flagella. On the contrary, kinesins from kinesin-5 and kinesin-13 families are important in mitosis where they generate forces or movement to position anti-parallel microtubules.

Kinesin and diseases

As mentioned above, member of kinesin family are mostly responsible for intracellular transport and mitosis. Consequently, kinesin related diseases can be classified as intracellular transportation malfunction, non-physiological cargo transportation and disease linked to uncontrollable cell proliferation. One example related to intra-cellular transport malfunction of kinesin is Charcot-Marie-Tooth (CMT) 2A disease. The cause of CMT is that KIF1B, a member of kinesin-3 family, is mutated in its motor domain, and synaptic vesicle precursors are not properly transported to the required synaptic termini. This malfunction leads to a progressive atrophy of distal muscles. Another example is relevant to kinesin-2 which is responsible to supplying protein component for cilia and flagella. Defect in kinesin-2 related transport cause polycystic kidney disease by affecting sensory cilia in the kidney, retinitis pigmentosa in which the transport for photoreceptors is malfunctioning and Kartagener's syndrome is characterized by abnormal sperm flagella, bronchial cilia and nodal cilia.

The second category of kinesin linked disease is non-physiological cargo transport. This non-physiological cargo transport involves certain viruses, bacteria or parasites. These pathogens hijack kinesin-dependent transport system to transport their compartment back to cell membrane. For example, vaccinia requires kinesin-1 motor to transport viral protein A36R, and herpes viruses interact with kinesin-1 for long distance transport from cell body to axon terminals. The third category of kinesin-related diseases is uncontrollable cell proliferation. The uncontrollable cell proliferation or cancer requires multiple mitosis steps to duplicate the cells. It is clear that number of kinesins involve in mitosis; therefore, one possible strategy to treat such cancers is to develop drug that target kinesin for chemotherapy. For example, the compound adociasulfate-2 can block kinesindependent motility and mitosis whereas another compound, monastrol, can inhibit Eg5, a member of kinesin-5 group of motors, and cause defect in cell division. Since these molecules can inhibit or modulate kinesin's function, they offer significant potential for future clinical applications.

Reference:

Kao, Ming-Tse.Kinesin: Directional properties, strain coordination and nanotechnology applications. Diss. The University of Michigan, 2009.

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