Model for microtubule chemotaxis

Abstract

Dramatic reorganization of the microtubule (MT) cytoskeleton underlies a number of cellular processes including mitosis and axon initiation. MT assembly in vivo is regulated by MT assembly modulators, which are themselves regulated, often by antagonistic kinase/phosphatase pairs such that the phosphorylated form is active while the dephosphorylated form is inactive. If the antagonistic activities are spatially segregated in the cell, then a stable gradient should exist to effectively promote MT assembly in one region and/or inhibit assembly in another region. This mechanism has been invoked to explain how MTs are recruited to chromosomes during mitosis. What is not known is under what conditions such gradients can be expected to exist in the cell. To quantitatively predict such gradients, a reaction-diffusion model of the kinase/phosphatase reactions was developed. Using typical reaction rate constants and diffusion coefficients, it was predicted that a 10-fold concentration change should exist over a 10 /spl mu/m distance. Such a gradient would be expected to exert a substantial Influence over MT assembly dynamics, effectively recruiting microtubules to a particular subregion of the cell. The recruitment mechanism is reminiscent of and analogous to bacterial chemotaxis, so I call it "microtubule chemotaxis".