Research Interests

Kayaoko Tanaka's Research Interests

Microtubule re-organisation and cell signalling associated with meiotic differentiation

 

Publications

Sexual differentiation involving mating and meiosis is fundamental to living organisms to achieve effective evolution. Gametes generated through meiosis contain a set of genetic materials, which are different from their parents, through extensive chromosome pairing and recombination, followed by two successive rounds of chromosome segregation without intervening DNA synthesis.

Our research aims to understand the highly coordinated sexual differentiation process. We focus on two subjects; (1) function and regulation of microtubules during meiotic prophase I and (2) the mechanism of cell signaling that triggers meiotic differentiation. We exploit genetically tractable fission yeast as a powerful model system to address these questions.

(1) Molecular mechanism of microtubule reorganization during sexual differentiation.

Nuclear movement that involves nuclear rotation and chromosome movement during meiotic prophase I is highly conserved from yeast to mammals. It facilitates pairing of homologous chromosomes, leading to efficient meiotic recombination. In many eukaryotes including fission yeast and mice, the movement is primarily driven by microtubule and associated motor proteins.

We showed that, during fission yeast meiotic prophase I, microtubules emanate from the area just above the yeast centrosome to form radial microtubule (rMT) structure (Fig. 1, Funaya et al., Curr. Biol., 22, 562-574 (2012)). We termed the area the radial microtubule organizing centre (rMTOC).

 

The rMTOC resembles the pericentriolar material (PCM) in higher eukaryotes in many ways: appearing as electron-dense structure by EM observation, being enriched in γ-tubulin within the structure, and harboring high MTOC activity (Fig2, Funaya et al., Curr. Biol., 22, 562-574 (2012)). We believe that rMTOC serves as a unique tractable model to study PCM biology.

Our projects involve identification of rMTOC components and exploration of mechanistic insights as to how rMTOC holds microtubule minus ends and how rMTOC is associated with the centrosome.

(2) Integrated understanding of RAS-mediated signaling pathways.

Fission yeast mating pheromone triggers the RAS signaling pathway essential for meiotic differentiation including mating and sporulation.

A model has been proposed that Ras1, the unique fission yeast RAS homologue, activates two downstream targets, the pheromone MAPK cascade and the Cdc42 morphological pathway, based on the result of yeast two hybrid analysis that Ras1 interacts with both MAPKKKByr2 and Scd1, a GDP-GTP exchange factor for Cdc42 (Chang et al., Cell, 79, 131-141, (1994)). However, direct in vivo biochemical evidence has been missing.

We established a condition to induce highly synchronous mating of haploid fission yeast cells and an assay system to directly measure the MAPKSpk1 activation status with an anti-phospho ERK monoclonal antibody. These tools allow us to precisely monitor the MAPKSpk1 activation status during the mating process in various mutant cells and to build up a model of Ras signaling. Our results support the original hypothesis that Ras1 activates two downstream pathways, the pheromone MAPK cascade and the Cdc42 morphological pathway (Fig. 3, manuscript in preparation). Furthermore, activation of these two pathways is not only necessary but also sufficient for successful pheromone response.

Fig. 3.  RAS signaling plays a key role in fission yeast sexual differentiation


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Department of Molecular and Cell Biology

T: +44(0)116 229 7038
E: MolCellBiol@le.ac.uk

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