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PreprintCited by 5Microtubule and mitosis dynamicsGenomics and Chromatin DynamicsCancer Treatment and Pharmacology

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Modification of the Neck Linker of KIF18A Alters Microtubule Subpopulation Preference

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Queen, Katelyn A., Cario, Alisa, Berger, Christopher L., Stumpff, Jason·2023·Molecular Biology of the Cell
DOI 10.1101/2023.05.02.539080PMC PMC10881168

Preprint — published as 10.1091/mbc.e23-05-0167 · Paper page

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Abstract

Kinesins support many diverse cellular processes, including facilitating cell division through mechanical regulation of the mitotic spindle. However, how kinesin activity is controlled to facilitate this process is not well understood. Interestingly, post-translational modifications have been identified within the enzymatic region of all 45 mammalian kinesins, but the significance of these modifications has gone largely unexplored. Given the critical role of the enzymatic region in facilitating nucleotide and microtubule binding, it may serve as a primary site for kinesin regulation. Consistent with this idea, a phosphomimetic mutation at S357 in the neck- linker of KIF18A alters the localization of KIF18A within the spindle from kinetochore microtubules to peripheral microtubules. Changes in localization of KIF18A-S357D are accompanied by defects in mitotic spindle positioning and the ability to promote mitotic progression. This altered localization pattern is mimicked by a shortened neck-linker mutant, suggesting that KIF18A-S357D may cause the motor to adopt a shortened neck-linker like state that prevents KIF18A from accumulating at the plus-ends of kinetochore microtubules. These findings demonstrate that post-translational modifications in the enzymatic region of kinesins could be important for biasing their localization to particular microtubule subpopulations.

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Metadata

Authors
Queen, K. A., Cario, A., Berger, C. L., & Stumpff, J.
Affiliations
University of Vermont (US)
Corresponding author
Stumpff, Jason
ORCID
Venue
Molecular Biology of the Cell
Publisher
openRxiv
Published
2023-05-02
Volume
35
Issue
1
Pages
ar3-ar3
ISSN
1059-1524 (ISSN-L)
DOI
10.1101/2023.05.02.539080
PMC
PMC10881168
OpenAlex
W4388017978
Cited by
5
References
1
Citations by year
2026: 3 · 2024: 1 · 2023: 1
FWCI
0.72
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Molecular Biology of the Cell (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by)
Funders
  • National Science Foundation (1842491)
  • National Institutes of Health (NIH-R01)
  • National Institute of General Medical Sciences (R01GM132646, R01GM130556, R01GM121491, R35GM144133)
  • National Institute of Neurological Disorders and Stroke (R01NS118513)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
Keywords
KIF18A, phosphomimetic mutations, post-translational modification, mitotic spindle positioning, kinetochore microtubules, mitotic progression

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