Dunn, S., Morrison, E. E., Liverpool, T. B., Molina-Paris , Carmen, Cross, R. A., Alonso, M. (Maria) and Peckham, M.. (2008) Differential trafficking of Kif5c on tyrosinated and detyrosinated microtubules in live cells. Journal of Cell Science, Vol.121 (No.7). pp. 1085-1095. ISSN 0021-9533

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Abstract

Kinesin-1 is a molecular transporter that trafficks along microtubules. There is some evidence that kinesin-1 targets specific cellular sites, but it is unclear how this spatial regulation is achieved. To investigate this process, we used a combination of in vivo imaging of kinesin heavy-chain Kif5c (an isoform of kinesin-1) fused to GFP, in vitro analyses and mathematical modelling. GFP-Kif5c fluorescent puncta localised to a subset of microtubules in live cells. These puncta moved at speeds of up to 1 μm second–1 and exchanged into cortically labelled clusters at microtubule ends. This behaviour depended on the presence of a functional motor domain, because a rigor-mutant GFP-Kif5c bound to microtubules but did not move along them. Further analysis indicated that the microtubule subset decorated by GFP-Kif5c was highly stable and primarily composed of detyrosinated tubulin. In vitro motility assays showed that the motor domain of Kif5c moved detyrosinated microtubules at significantly lower velocities than tyrosinated (unmodified) microtubules. Mathematical modelling predicted that a small increase in detyrosination would bias kinesin-1 occupancy towards detyrosinated microtubules. These data suggest that kinesin-1 preferentially binds to and trafficks on detyrosinated microtubules in vivo, providing a potential basis for the spatial targeting of kinesin-1-based cargo transport.

Item Type:	Journal Article
Subjects:	Q Science > QH Natural history > QH301 Biology Q Science > QP Physiology
Divisions:	Faculty of Medicine > Warwick Medical School > Biomedical Cell Biology Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Microtubules, Cytology -- Research, Kinesin
Journal or Publication Title:	Journal of Cell Science
Publisher:	The Company of Biologists Ltd.
ISSN:	0021-9533
Official Date:	April 2008
Volume:	Vol.121
Number:	No.7
Page Range:	pp. 1085-1095
Identification Number:	10.1242/jcs.026492
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Funder:	Wellcome Trust (London, England), Cancer Research UK (CRUK), Marie Curie Memorial Foundation
URI:	http://wrap.warwick.ac.uk/id/eprint/36902

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