Remote control of microtubule plus-end dynamics and function from the minus-end.

Xiuzhen Chen,Marcel M Stangier,Michel O Steinmetz,Lukas A Widmer,Yves Barral,Jörg Stelling

doi:10.7554/elife.48627

Xiuzhen Chen, Marcel M Stangier + Show 4 more

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https://doi.org/10.7554/elife.48627

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Abstract

In eukaryotes, the organization and function of the microtubule cytoskeleton depend on the allocation of different roles to individual microtubules. For example, many asymmetrically dividing cells differentially specify microtubule behavior at old and new centrosomes. Here we show that yeast spindle pole bodies (SPBs, yeast centrosomes) differentially control the plus-end dynamics and cargoes of their astral microtubules, remotely from the minus-end. The old SPB recruits the kinesin motor protein Kip2, which then translocates to the plus-end of the emanating microtubules, promotes their extension and delivers dynein into the bud. Kip2 recruitment at the SPB depends on Bub2 and Bfa1, and phosphorylation of cytoplasmic Kip2 prevents random lattice binding. Releasing Kip2 of its control by SPBs equalizes its distribution, the length of microtubules and dynein distribution between the mother cell and its bud. These observations reveal that microtubule organizing centers use minus to plus-end directed remote control to individualize microtubule function.

Highlights

Microtubules are hollow cylinders formed by the polymerization of ab-tubulin dimers
The minus-end of most microtubules is stabilized by a V-tubulin cap, which tethers microtubule minus-ends to microtubule organizing centers (MTOCs) such as centrosomes in animal cells and spindle pole bodies (SPBs) in fungi and many protists (Sanchez and Feldman, 2017)
In agreement with published in vitro data (Varga et al, 2006; Varga et al, 2009), Kip3-3xsfGFP intensity increased along cytoplasmic microtubules, the protein being barely detectable at their minus-ends and reaching maximal levels at the plus-ends (Figure 1a; note that the abundant GFP fluorescence around the SPB originated from Kip3-3xsfGFP on the nuclear spindle microtubules)

Summary

Introduction

Microtubules are hollow cylinders formed by the polymerization of ab-tubulin dimers Throughout eukaryotes, they drive mitotic chromosome segregation, form cilia and flagella, and function in cell polarity (Desai and Mitchison, 1997). The microtubule plus-end grows away from the MTOC and explores the cellular space by dynamically alternating between periods of growth and shrinkage, a process called dynamic instability (Mitchison and Kirschner, 1984). This search function allows microtubules to reach attachment sites, for example, kinetochores on chromosomes or various cortical sites (Akhmanova and Steinmetz, 2008; Kirschner and Mitchison, 1986)

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