Messin, Liam J. (2017) Spatial control of microtubule shrinkage. PhD thesis, University of Warwick.

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Abstract

Microtubules are long linear polymers that switch randomly between periods of growth and shrinkage, in a process known as dynamic instability. In vivo, dynamic instability is regulated by microtubule associated proteins (MAPs). One class of MAPS, the kinesins, move actively along microtubules, and some regulate microtubule dynamics. Kinesin-8, a kinesin, regulates microtubule dynamics in a wide range of eukaryotic cells.

Schizosaccharomyces pombe (S. pombe) provides a well-characterised system in which to study microtubule regulation by MAPs. During interphase, microtubules grow from the centre of the rod-shaped cell until their plus ends reach and pause at the cell end, before undergoing catastrophe and shrinking. Shrinkage occurs predominantly at cell ends, even as the cell grows longer.

I have studied the cell biology of kinesin-8-dependent interphase microtubule dynamics in S. pombe. I have identified an interphase-specific binding partner of S. pombe kinesin-8 (Klp5/Klp6); Mcp1. Mcp1 was required for Klp5/Klp6 accumulation at interphase microtubule plus ends and for Klp5/Klp6 induced interphase microtubule shrinkage.

Tea2 (a kinesin) and Tip1 (CLIP170 orthologue) were found to stabilise interphase microtubules. Cells lacking Tea2 or Tip1 displayed interphase microtubules which, after reaching cell ends, underwent shrinkage sooner than wild type cells. Cells lacking Klp5/Klp6 or Mcp1 showed the opposite phenotype, microtubules which dwelt at cell ends longer than control cells before shrinking.

Klp5/Klp6 accumulation on interphase microtubule plus ends steadily increased, peaking just before microtubule shrinkage. In contrast, Tea2 accumulated rapidly to newly nucleated interphase microtubule plus ends and was lost before microtubule shrinkage. I propose a model in which Tea2 prevents Klp5/Klp6 induced microtubule shrinkage until the interphase microtubule has grown to the cell end, where Tea2 is lost. At the cell end Klp5/Klp6 now induce shrinkage.

Item Type:	Thesis or Dissertation (PhD)
Subjects:	Q Science > QH Natural history > QH301 Biology
Library of Congress Subject Headings (LCSH):	Microtubules, Kinesin, Schizosaccharomyces pombe -- Cytology
Official Date:	July 2017
Dates:	Date Event July 2017 Submitted
Institution:	University of Warwick
Theses Department:	Warwick Medical School
Thesis Type:	PhD
Publication Status:	Unpublished
Supervisor(s)/Advisor:	Millar, Jonathan B. A. ; Cross, R. A.
Format of File:	pdf
Extent:	xiv, 259 leaves : illustrations, charts
Language:	eng

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