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Cited by 166Microtubule and mitosis dynamicsGenetic and Kidney Cyst DiseasesCancer Treatment and Pharmacology

MAP7 family proteins regulate kinesin-1 recruitment and activation

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Hooikaas, Peter Jan, Martin, Maud, Mühlethaler, Tobias, Kuijntjes, Gert-Jan, Peeters, Cathelijn A.E., Katrukha, Eugene A., Ferrari, Luca, Stucchi, Riccardo +9 more·2019·Journal of Cell Biology
DOI 10.1083/jcb.201808065PMC PMC6446838

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Abstract

Kinesin-1 is responsible for microtubule-based transport of numerous cellular cargoes. Here, we explored the regulation of kinesin-1 by MAP7 proteins. We found that all four mammalian MAP7 family members bind to kinesin-1. In HeLa cells, MAP7, MAP7D1, and MAP7D3 act redundantly to enable kinesin-1–dependent transport and microtubule recruitment of the truncated kinesin-1 KIF5B-560, which contains the stalk but not the cargo-binding and autoregulatory regions. In vitro, purified MAP7 and MAP7D3 increase microtubule landing rate and processivity of kinesin-1 through transient association with the motor. MAP7 proteins promote binding of kinesin-1 to microtubules both directly, through the N-terminal microtubule-binding domain and unstructured linker region, and indirectly, through an allosteric effect exerted by the kinesin-binding C-terminal domain. Compared with MAP7, MAP7D3 has a higher affinity for kinesin-1 and a lower affinity for microtubules and, unlike MAP7, can be cotransported with the motor. We propose that MAP7 proteins are microtubule-tethered kinesin-1 activators, with which the motor transiently interacts as it moves along microtubules.

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  • Distribution of mitochondria throughout the cell is Kinesin-1-dependent, and absence of Kinesin-1 or its activating MAP, MAP7, leads to clustering of mitochondria around the nucleus.

    “Distribution of mitochondria throughout the cell is Kinesin-1–dependent and the absence of Kinesin-1 or its activating MAP, MAP7, leads to the clustering of mitochondria around the nucleus.”

    From A live-cell marker to visualize the dynamics of stable microtubules throughout the cell cycle (2023) · cites this paper as Hooikaas et al., 2019

    The Results section reports that loss of the kinesin-1 motor KIF5B caused mitochondria to cluster around the nucleus in HeLa cells. It also says that loss of MAP7 alone caused no mitochondrial-localization defect; clustering occurred when MAP7, MAP7D1, and MAP7D3 were depleted together. (LLM, conf=0.90)

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Authors
Hooikaas, P. J., Martin, M., Mühlethaler, T., Kuijntjes, G.-J., Peeters, C. A. E., Katrukha, E. A., Ferrari, L., Stucchi, R., Verhagen, D. G. F., van Riel, W. E., Grigoriev, I., Altelaar, A. F. M., Hoogenraad, C. C., Rüdiger, S. G. D., Steinmetz, M. O., Kapitein, L. C., & Akhmanova, A.
Affiliations
  • Utrecht University (NL)
  • Paul Scherrer Institute (CH)
  • Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Utrecht, Netherlands 1
  • Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research, Utrecht Institute for Pharmaceutical Sciences and The Netherlands Proteomics Centre, Utrecht University, Utrecht, Netherlands 4
  • University of Basel (CH)
Corresponding author
Akhmanova, Anna
ORCID
Venue
Journal of Cell Biology
Publisher
Rockefeller University Press
Published
2019-02-15
Volume
218
Issue
4
Pages
1298-1318
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
DOI
10.1083/jcb.201808065
PMC
PMC6446838
OpenAlex
W2913674846
Cited by
166
References
7
Citations by year
2026: 24 · 2025: 25 · 2024: 18 · 2023: 26 · 2022: 19 · 2021: 17 · 2020: 24 · 2019: 13
FWCI
9.59
Type
journal article
Language
en
Open access
Licence
Locations
  • The Journal of Cell Biology (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DORA PSI (Paul Scherrer Institute) (submittedVersion, cc-by)
  • Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
  • Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
Funders
  • European Research Council (609822)
  • Netherlands Organization for Scientific Research (824.15.017)
  • Marie Curie
  • Swiss National Science Foundation (31003A_166608)
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
kinesin-1, MAP7, microtubule transport, microtubule binding, allosteric regulation, motor protein regulation, cotransport
MeSH terms
Animals, Benzamides, Chlorocebus aethiops, Enzyme Activation, HeLa Cells, Humans, Microtubule-Associated Proteins, Microtubules, Mitochondria, Protein Binding, Kinesins, COS Cells, Protein Transport, Diketopiperazines, Protein Interaction Domains and Motifs, HEK293 Cells

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