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Cited by 4Genetic and Kidney Cyst DiseasesMicrotubule and mitosis dynamicsCystic Fibrosis Research Advances

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Kinesin-2 autoinhibition requires elbow phosphorylation

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Chen, Guanghan, Guo, Zhengyang, Zhu, Zhiwen, Xie, Shanshan, Zhou, Tianhua, Ou, Guangshuo·2025·eLife
DOI 10.7554/elife.103648.3PMC PMC12158429

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Abstract

Kinesin motor proteins facilitate microtubule-based transport by converting chemical energy into mechanical forces, but this activity is autoinhibited until cargo is loaded. Regulatory mechanisms underlying this autoinhibitory conformation are not well understood. Here, we show that a NEver in mitosis Kinase NEKL-3 directly phosphorylates a flexible elbow region between two coiled-coil domains connecting the motor head and tail of an intraflagellar transport kinesin, OSM-3. The phosphor-dead (PD) mutation, but not phosphor-mimic (PM) mutation, induces constitutive motility of OSM-3 in vitro. Using knock-in animals, we discovered that both PD and PM mutations shorten the C. elegans sensory cilia. The constitutively active OSM-3PD fails to enter cilia and abnormally accumulates in neurites, mimicking another hyperactive mutation, OSM-3G444E. Conversely, OSM-3PM enters cilia but moves at a reduced speed, indicating an inhibitory role of elbow phosphorylation in kinesin motility. These findings highlight the crucial role of elbow phosphorylation in regulating kinesin autoinhibition.

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Metadata

Authors
Chen, G., Guo, Z., Zhu, Z., Xie, S., Zhou, T., & Ou, G.
Affiliations
  • Tsinghua University (CN)
  • Soochow University (CN)
  • Children's Hospital of Zhejiang University (CN)
  • Zhejiang University (CN)
Corresponding author
Chen, Guanghan
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2025-06-11
Volume
13
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.103648.3
PMC
PMC12158429
OpenAlex
W4403185656
Cited by
4
References
6
Citations by year
2026: 3 · 2025: 1
Type
posted content
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Natural Science Foundation of China (31991191)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
Keywords
intraflagellar transport, sensory cilia, microtubule transport, Caenorhabditis elegans, ciliary motility, motor protein regulation
MeSH terms
NIMA-Related Kinases, Animals, Cilia, Mutation, Phosphorylation, Kinesins, Caenorhabditis elegans, Caenorhabditis elegans Proteins

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