Microtubules can grow by addition of a GTP-tubulin, mostly at the plus end. Conversely, release of GDP-tubulin leads to shrinkage of microtubules. New microtubules are preferentially nucleated at the γ-tubulin ring complex. Hence, the location and concentration of GTP-tubulin building blocks and γ-tubulin ring complexes are two factors that can affect microtubule nucleation and growth. Cortical microtubule pattern formation does not begin at a blank membrane, but rather at a membrane that is already seeded with a pre-pattern of microtubules established during an earlier phase of cell differentiation. Thus, pattern formation is the result of changes in microtubule turnover that generate locations of higher and lower densities. Previous models that have taken into account that nucleation of new microtubules occurs mostly at pre-existing microtubules (density-dependent nucleation) ran into the inhomogeneity problem, in which positive feedback excessively increased local densities at the expense of other regions that became depleted. Therefore, something needs to limit the increasing density to counteract this positive feedback.
Jacobs and colleagues show that the microtubule density is limited not by depletion of the GTP-tubulin pool but rather by the saturation of nucleation complex recruitment. Diffusion of GTP-tubulin was too fast to explain attenuated density increase by depletion of GTP-tubulin, even when not considering cytoplasmic streaming. Instead, the recruitment of γ-tubulin ring complexes to microtubules appears to be a limiting factor. These complexes are preferentially inserted close to pre-existing microtubules, so the competition for nucleation complexes is reduced to denser regions resulting in a saturation effect that can counteract the positive feedback of ever-increasing microtubule density.
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