Peet, Daniel R. (2015) Mechanical inhibition of microtubule depolymerisation by kinesin. PhD thesis, University of Warwick.

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Abstract

Kinesin-driven transport of molecular cargo along microtubules is central to the self-organisation of eukaryotic cells. We investigated the effect of kinesin-1 on microtubule stability using in vitro techniques. We found that kinesin-1, which was previously reported to have no influence on microtubule dynamics, to reduce shrinkage rates by approximately two orders of magnitude if maintained in a nucleotide-free or ATP-bound state. No effect was observed in the presence of high ADP concentrations, indicating that the microtubule-stabilising ability of kinesin-1 is constrained to a subset of the kinetic states of its ATPase cycle. By decorating just one side of the microtubule lattice with kinesin, we were able to gain additional insights into the mechanics of microtubules. By stabilising just 2-3 protofilaments with kinesin, the structural integrity of most of the microtubule could be maintained. Curiously, in such circumstances the microtubule would split at its ends. We further showed that microtubule curvature induced by hydrodynamic flow is trapped or even increased by nucleotide-free kinesin. We propose a mechanism whereby kinesin-1 drives the conformation of polymerised GDP-tubulin into a slightly elongated and shrinkage-resistant conformation. This is essentially the converse mechanism of that reported for the kinesin-13, MCAK, which supports tubulin in a curved conformation that is incompatible with the microtubule lattice.

Item Type:	Thesis (PhD)
Subjects:	Q Science > QH Natural history > QH301 Biology
Library of Congress Subject Headings (LCSH):	Kinesin
Official Date:	September 2015
Dates:	Date Event September 2015 UNSPECIFIED
Institution:	University of Warwick
Theses Department:	Systems Biology Doctoral Training Centre
Thesis Type:	PhD
Publication Status:	Unpublished
Supervisor(s)/Advisor:	Cross, R. A. ; Burroughs, Nigel John
Sponsors:	Biotechnology and Biological Sciences Research Council (Great Britain)
Extent:	xi, 134 pages : illustrations, charts
Language:	eng

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