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bioRxiv · 10.1101/690651

MTOC clustering and nuclear division through proper spindle positioning in yeast: a microtubule grow-and-catch model

Chatterjee, S.·Som, S.·Varshney, N.·Sanyal, K.·Paul, R.
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Abstract

The dynamic process of mitotic spindle assembly depends on multitudes of inter-dependent interactions involving kinetochores (KTs), microtubules (MTs), spindle pole bodies (SPBs), and molecular motors. Before forming the mitotic spindle, multiple visible microtubule organizing centers (MTOCs) coalesce into a single focus to serve as a SPB in the pathogenic budding yeast, Cryptococcus neoformans. To explain this unusual phenomenon in the fungal kingdom, we propose a search and capture model, in which cytoplasmic MTs (cMTs) nucleated by MTOCs grow and capture each other to promote MTOC clustering. Our quantitative modeling identifies multiple redundant mechanisms mediated by a combination of cMT-cell cortex interactions and inter-cMT coupling to facilitate MTOC clustering within the physiological time limit as determined by time-lapse live-cell microscopy. Besides, we screen various possible mechanisms by computational modeling and propose optimal conditions that favor proper spindle positioning - a critical determinant for timely chromosome segregation. These analyses also reveal that a combined effect of MT buckling, dynein pull, and cortical push maintains spatiotemporal spindle localization.

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Chatterjee, S., Som, S., Varshney, N., Sanyal, K., Paul, R.. 2019-07-04. MTOC clustering and nuclear division through proper spindle positioning in yeast: a microtubule grow-and-catch model. https://doi.org/10.1101/690651

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