A model for the microtubule organizing activity of the centrosomes and kinetochores in mammalian cells

Abstract In this report I review shortly recent evidence on the role of centrosomes and kinetochores in organized microtubule assembly in cells. I arrive at the conclusion that models for these organizing centres must provide an explanation for the following observations: 1. 1. Both centrosomes and kinetochores induce microtubule assembly in their immediate vicinity at a tubulin concentration below the cytoplasmic critical concentration. 2. 2. Initially, the newly assembled microtubules are not necessarily anchored to the MTOC's. 3. 3. The assembly initiating and microtubule stabilizing activity of the MTOC's is abrogated by lowering the critical tubulin concentration in the cytoplasm. 4. 4. Microtubules attach to the centrosomes with their minus end and to the kinetochores with their plus end. 5. 5. Interactions between centrosomes and kinetochores or microtubules derived from them are important in guiding microtubule elongation and stabilizing kinetically unfavored microtubule sets (kinetochore microtubules). Models that are based on the presence of seeds or templates in the MTOC's do not predict observations 2 and 3. Models which conceive MTOC's as sites where microtubules are anchored at their minus end which is consequently capped do not predict observations 3 and 4. We propose a model that explains all the observations summarized above. Both centrosomes and kinetochores induce assembly at low tubulin concentrations by being domains where the critical tubulin concentration is lower than elsewhere in the cytoplasm. Once formed, microtubules may become more or less securely fixed to the MTOC by their minus (centrosome) or plus end (kinetochore). Because this anchoring may occur through lateral bonds between the microtubule surface and a component of the MTOC the end can remain free to add or loose subunits. The model allows cells to build microtubule sets of different polarity and stability. Unlike the seed and minus end capping models it is compatible with mechanisms of intracellular motility based on microtubule treadmilling.