September 15, 2007

Microtubules: The Cytoskeletal Rail-Road

The cells have a rich cytoskeletal network, consisting of microfilaments, microtubules, intermediate filaments, and proteins that hold them to the interior of the cell. These cytoskeletal structures subserve various functions such as giving the cells its shape and allows small organelles inside the cells to go to other places in the cells. For example, in a nerve cell, the synaptic vesicles, which contain neurotransmitters, are synthesized in the cell bodies. These neurotransmitter filled vesicles are then transported by 'molecular motors' form the cell body to the synaptic knobs, situated at the other end of the neuron.

Not only do they (microtubules) serve as a 'rail line' on which molecular motors move (walk), they also act as 'traction wires' which pull chromosomes apart during cell division (mitosis). Thus in cancer, when cell division is excessive, drugs which interfere with microtubule formation (polymerization) can be employed effectively to curb this cell replication gone haywire. Vinca alkaloids (obtained from the Vinca rosea plant) such as vincristine (used in Hodgkin's Lymphoma, small cell lung cancer etc.), vinblastine (used in ALL or acute lymphoblastic leukemia in children), vinorelbine (used in NSCLC or non small cell carcinoma of the lung); and taxanes such as taxol (paclitaxel, used for the treatment of cancers of the breast and ovary) extracted from the western yew tree, are molecules which stabilize microtubules and thus arrest cell division.

Microtubules are composed of smaller subunits made of proteins, alpha tubulin and beta tubulin. Alpha and beta tubulins together form a heterodimer (hetero since alpha and beta tubulins are different molecules). 13 such hetero dimers join to form a ring and many such rings are joined in a stacked manner to form this hollow structure called microtubules. Microtubules are dynamic structures with one end forming by polymerization (+end) and the other end destroying by depolymerization (-end), as this 10 second video clip illustrates.
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