2. Academic Validation
  3. Kinesin-1 coordinates cross-talk between microtubule and actin cytoskeletons during dendritic cell migration

Kinesin-1 coordinates cross-talk between microtubule and actin cytoskeletons during dendritic cell migration

  • Sci Adv. 2025 Oct 17;11(42):eadx7672. doi: 10.1126/sciadv.adx7672.
Pierre Duquesne 1,  Céline Aoun 1,  Mathieu Kurowska 1,  Brieuc P Perot 2,  Kerui Zhang 1,  Mounia Debili 1,  Mirjana Weimershaus 3,  François-Xavier Mauvais 4,  Nicolas Cagnard 5,  Nicolas Goudin 5,  Bernardita Medel 1,  Juan Eduardo Montero-Hermández 1,  Linda Diedhiou 1,  Jian-Dong Huang 6,  Alain Fischer 1 7 8,  Geneviève de Saint Basile 1,  Mickaël M Ménager 2,  Pablo Vargas 9,  Fernando E Sepulveda 1 10,  Gaël Ménasché 1
Affiliations

Affiliations

  • 1 Université Paris Cité, Imagine Institute, Laboratory of Molecular Basis of Altered Immune Homeostasis, INSERM UMR1163, F-75015 Paris, France.
  • 2 Université Paris Cité, Imagine Institute, Laboratory of Single-Cell Inflammatory Responses and Multi-OMICs Networks, INSERM UMR1163, F-75015 Paris, France.
  • 3 Institute of Functional Genomics (IGF), CNRS UMR 5203, INSERM U1191, Université de Montpellier, Montpellier, France.
  • 4 Université Paris Cité, INSERM UMR1141, NeuroDiderot, Institut Hospitalo-Universitaire Robert-Debré du Cerveau de l'Enfant, Paris, France.
  • 5 Structure Fédérative de Recherche Necker, INSERM US24/CNRS UAR3633, Université Paris Cité, Institut Imagine, F-75015 Paris, France.
  • 6 School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
  • 7 Immunology and Pediatric Hematology Department, Necker Children's Hospital, AP-HP, F-75015 Paris, France.
  • 8 Collège de France, F-75005 Paris, France.
  • 9 Leukomotion Lab, Paris Cité University, INSERM UMR-S1151, CNRS UMR-S8253, Institut Necker Enfants Malades, F-75015 Paris, France.
  • 10 Centre National de la Recherche Scientifique (CNRS), F-75015 Paris, France.
PMID: 41105759 DOI: 10.1126/sciadv.adx7672
Abstract

Dendritic cells (DCs) are professional antigen (Ag)-presenting cells that excel in initiating adaptive immune responses by continuously scanning peripheral tissues for Ags. To facilitate efficient DC migration, constant cross-talk between actin and microtubules is required to coordinate cytoskeletal networks and actomyosin contractility, but the related mechanisms have not been extensively characterized. We show that mouse DCs lacking Kif5b (the heavy chain of kinesin-1) exhibit a major impairment in cell migration in vivo and in vitro. Mechanistically, kinesin-1 coordinates cytoskeletal cross-talk between actin and microtubules during DC migration by modulating negatively RhoA activity through its interaction with GEF-H1, thereby limiting GEF-H1's availability in the cytosol. The same mechanism operates in human primary monocyte-derived DCs and regulates efficient migration in a confined environment. Thus, our results highlight kinesin-1 as a key regulator of DC migration, through its coordinated control of cytoskeletal dynamics.

Figures
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  • HY-112842
    99.64%, Rac/Cdc42 抑制剂
    Ras; CDK
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