Functional analysis of matrix that supports microtubule anchoring

Microtubules (MTs) are directional hollow tubular structure. They dynamically grow and shrink at their “plus” ends and convey fundamental cellular activities. The other MT end, the “minus” end, is capped with a protein complex called the -Tubulin complex (-TuC). Extensive research has proposed that the -TuC acts as a MT nucleation template and, hence, determines the directional MT growth. The -TuC is found accumulated at the major MT organizing centre (MTOC), the centrosome, from where MTs emanate.
Electron microscopy found that the centrosome consists of two barrel-shaped structures called centrioles and their surrounding amorphous matrix called pericentriolar material (PCM). It is the PCM, from which most cellular microtubules (MTs) emanate. Extensive studies showed that the PCM is enriched in numbers of proteins and the size of PCM is rigorously regulated. However, little is known about the PCM matrix structure at a molecular level and how it holds the minus ends of MTs. We explore biochemical properties of the PCM in order to reveal how the PCM matrix is composed and how the MT minus ends are anchored in the PCM. We then examine significance of the MT anchorage in regulating dynamic nuclear movement, which is observed in various organisms and differentiation stages including neural progenitor cells during brain development.
Throughout the project, we exploit highly tractable fission yeast as a model system that allows us to take multidisciplinary approaches. The centrosome equivalent in fungi is the spindle pole body (SPB). Recently, we found that during the fission yeast meiotic prophase, amorphous structure transiently appears next to the SPB and acts as the major MTOC. We named the structure the radial microtubule organising centre (rMTOC) as it organises radial microtubule (rMT) array. With help of dynein-dynactin complex, rMTOC drives vigorous nuclear movement. A protein called Hrs1, which is essential for the nuclear movement, is the major structural component of rMTOC.
rMTOC resembles the PCM in many ways; appearing as amorphous structure by EM observation, being enriched in -tubulin within the structure, and harbouring high MTOC activity. Hence the rMTOC provides a unique opportunity to study PCM biology. The system also serves as a powerful model for nuclear movement.


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