Differential trafficking of Kif5c on tyrosinated and detyrosinated microtubules in live cells

Sarah Dunn, Ewan E. Morisson, Tanniemola B. Liverpool, Carmen Molina-París, Robert A. Cross, Maria C. Alonso, Michelle Peckham*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

148 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1085-1095
Number of pages11
JournalJournal of Cell Science
Volume121
Issue number7
DOIs
Publication statusPublished - 1 Apr 2008

Keywords

  • Detyrosinated microtubules
  • Kinesin-1
  • Microtubules
  • Trafficking

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