Differential trafficking of Kif5c on tyrosinated and detyrosinated microtubules in live cells
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.
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Kinesin-1 moves preferentially along stable microtubules enriched in acetylation and detyrosination.
“Given the intrinsic property of Kinesin-1 to move selectively along the subset of MTs enriched in acetylation and detyrosination (Cai et al., 2009; Dunn et al., 2008; Liao and Gundersen 1998; Kaul et al., 2014), we set out to test the application of rigor Kinesin-1 as a marker for stable MTs.”
From A live-cell marker to visualize the dynamics of stable microtubules throughout the cell cycle (2023) · cites this paper as Dunn et al., 2008
Cites
Shaner, N. C., Campbell, R. E., Steinbach, P. A., Giepmans, B. N. G., Palmer, A. E., & Tsien, R. Y. (2004) · Nature Biotechnology · doi:10.1038/nbt1037 · Cited by 4,619 · see citing works
Identification of a novel force-generating protein, kinesin, involved in microtubule-based motility
VALE, R., REESE, T., & SHEETZ, M. (1985) · Cell · doi:10.1016/s0092-8674(85)80099-4 · Cited by 1,993 · cited 2× · see citing works
“Kinesin-1 (conventional kinesin) (Brady, 1985; Vale et al., 1985a ) moves towards the plus ends of MTs in vitro (Vale et al., 1985b).”
BackgroundThe Molecular Motor Toolbox for Intracellular Transport
Vale, R. D. (2003) · Cell · doi:10.1016/s0092-8674(03)00111-9 · Cited by 1,982 · see citing works
Direct observation of kinesin stepping by optical trapping interferometry
Svoboda, K., Schmidt, C. F., Schnapp, B. J., & Block, S. M. (1993) · Nature · doi:10.1038/365721a0 · Cited by 1,910 · see citing works
Microtubules containing acetylated alpha-tubulin in mammalian cells in culture.
Piperno, G., LeDizet, M., & Chang, X. J. (1987) · The Journal of cell biology · doi:10.1083/jcb.104.2.289 · Cited by 873 · see citing works
Kinesin Takes One 8-nm Step for Each ATP That It Hydrolyzes
Coy, D. L., Wagenbach, M., & Howard, J. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.6.3667 · Cited by 390 · see citing works
Kinesin׳s tail domain is an inhibitory regulator of the motor domain
Coy, D. L., Hancock, W. O., Wagenbach, M., & Howard, J. (1999) · Nature Cell Biology · doi:10.1038/13001 · Cited by 329 · see citing works
Kinesin undergoes a 9 S to 6 S conformational transition
Hackney, D. D., Levitt, J. D., & Suhan, J. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)42499-4 · Cited by 175 · see citing works
What kinesin does at roadblocks: the coordination mechanism for molecular walking
Crevel, I. M., Nyitrai, M., Alonso, M. C., Weiss, S., Geeves, M. A., & Cross, R. A. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600042 · Cited by 88 · see citing works
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Traffic control: regulation of kinesin motors
Verhey, K. J., & Hammond, J. W. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2782 · Cited by 546 · see citing works
Chen, Y., & Sheng, Z.-H. (2013) · Journal of Cell Biology · doi:10.1083/jcb.201302040 · Cited by 250 · see citing works
Kinesin Assembly and Movement in Cells
Verhey, K. J., Kaul, N., & Soppina, V. (2011) · Annual Review of Biophysics · doi:10.1146/annurev-biophys-042910-155310 · Cited by 231 · see citing works
Detyrosinated microtubules spatially constrain lysosomes facilitating lysosome-autophagosome fusion
Mohan, N., Sorokina, E. M., Verdeny, I. V., Alvarez, A. S., & Lakadamyali, M. (2019) · Journal of Cell Biology · doi:10.1083/jcb.201807124 · Cited by 92 · see citing works
A live-cell marker to visualize the dynamics of stable microtubules throughout the cell cycle
Jansen, K. I., Iwanski, M. K., Burute, M., & Kapitein, L. C. (2023) · Journal of Cell Biology · doi:10.1083/jcb.202106105 · Cited by 39 · see citing works
StableMARK-decorated microtubules in cells have expanded lattices
de Jager, L., Jansen, K. I., Hoogebeen, R., Akhmanova, A., Kapitein, L. C., Förster, F., & Howes, S. C. (2025) · Journal of Cell Biology · doi:10.1083/jcb.202206143 · Cited by 25 · see citing works
- Authors
- Dunn, S., Morrison, E. E., Liverpool, T. B., Molina-París, C., Cross, R. A., Alonso, M. C., & Peckham, M.
- Affiliations
- University of Leeds (GB)
- St James's University Hospital (GB)
- Applied Mathematics (School of Mathematics) University of Leeds, Leeds, LS2 9JT, UK
- Marie Curie (GB)
- Molecular Motors Group, Marie Curie Research Institute, The Chart, Oxted, Surrey, RH8 0TL, UK
- Corresponding author
- Peckham, Michelle
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2008-04-01
- Volume
- 121
- Issue
- 7
- Pages
- 1085-1095
- ISSN
- 0021-9533 (ISSN-L)
- 1477-9137
- OpenAlex
- W2147332958
- Cited by
- 242
- References
- 9
- Citations by year
- 2026: 10 · 2025: 15 · 2024: 14 · 2023: 11 · 2022: 11 · 2021: 13 · 2020: 11 · 2019: 15 · 2018: 13 · 2017: 10 · 2016: 15 · 2015: 13 · 2014: 15 · 2013: 14 · 2012: 12
- FWCI
- 6.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cell Science (publishedVersion)
- PubMed (publishedVersion)
- Explore Bristol Research (submittedVersion)
- Funders
- Wellcome Trust
- Cancer Research UK
- Biotechnology and Biological Sciences Research Council (BB/D524875/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
- Keywords
- KIF5C, kinesin-1, microtubule detyrosination, kinesin motor domain, freight transport, microtubule stability
- MeSH terms
- Animals, Cell Line, Chlorocebus aethiops, HeLa Cells, Humans, Immunohistochemistry, Microtubules, Models, Biological, Protein Binding, Tyrosine, Kinesins, COS Cells, Protein Transport, Mice
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