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Cited by 156Microtubule and mitosis dynamicsCellular transport and secretionCancer Treatment and Pharmacology

Preferential binding of a kinesin-1 motor to GTP-tubulin–rich microtubules underlies polarized vesicle transport

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Nakata, Takao, Niwa, Shinsuke, Okada, Yasushi, Perez, Franck, Hirokawa, Nobutaka·2011·Journal of Cell Biology
DOI 10.1083/jcb.201104034PMC PMC3144414
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Abstract

Polarized transport in neurons is fundamental for the formation of neuronal circuitry. A motor domain–containing truncated KIF5 (a kinesin-1) recognizes axonal microtubules, which are enriched in EB1 binding sites, and selectively accumulates at the tips of axons. However, it remains unknown what cue KIF5 recognizes to result in this selective accumulation. We found that axonal microtubules were preferentially stained by the anti–GTP-tubulin antibody hMB11. Super-resolution microscopy combined with EM immunocytochemistry revealed that hMB11 was localized at KIF5 attachment sites. In addition, EB1, which binds preferentially to guanylyl-methylene-diphosphate (GMPCPP) microtubules in vitro, recognized hMB11 binding sites on axonal microtubules. Further, expression of hMB11 antibody in neurons disrupted the selective accumulation of truncated KIF5 in the axon tips. In vitro studies revealed approximately threefold stronger binding of KIF5 motor head to GMPCPP microtubules than to GDP microtubules. Collectively, these data suggest that the abundance of GTP-tubulin in axonal microtubules may underlie selective KIF5 localization and polarized axonal vesicular transport.

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  • Such regional variation is consistent with previous studies and suggests that lattice conformation can be locally influenced by lattice-binding microtubule-associated proteins, post-translational modifications, mechanical stress, or repair processes.

    “Such regional variation is consistent with previous studies58and suggest that lattice conformation can be locally influenced by lattice-binding microtuble-associated proteins (MAPs)59–61, post-translational modifications, mechanical stress50,51, or repair processes62–66.”

    From Ghost Neuron preparation unlocks high-resolution structural mapping of intracellular architecture in axons (2026) · cites this paper as [61]

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Authors
Nakata, T., Niwa, S., Okada, Y., Perez, F., & Hirokawa, N.
Affiliations
  • Tokyo Medical and Dental University (JP)
  • The University of Tokyo (JP)
  • Centre National de la Recherche Scientifique (FR)
Corresponding author
Hirokawa, Nobutaka
ORCID
Venue
Journal of Cell Biology
Publisher
Rockefeller University Press
Published
2011-07-18
Volume
194
Issue
2
Pages
245-255
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
DOI
10.1083/jcb.201104034
PMC
PMC3144414
OpenAlex
W2052261649
Cited by
156
References
1
Citations by year
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FWCI
5.91
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Funders
  • Ministry of Education, Culture, Sports, Science and Technology
  • Japan Society for the Promotion of Science (21590211, 23000013)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
Keywords
kinesin-1, KIF5, axonal microtubules, EB1, GMPCPP, neuronal transport, super-resolution microscopy
MeSH terms
Animals, Antibodies, Axons, Biological Transport, Guanosine Triphosphate, Microtubule-Associated Proteins, Microtubules, Swine, Tubulin, Kinesins, Mice

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