Kinesin-1 coordinates cross-talk between microtubule and actin cytoskeletons during dendritic cell migration
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.
Authors
- François‐Xavier Mauvais (ORCID: https://orcid.org/0000-0002-5240-4280)
- Mickaël Ménager
- Nicolas Cagnard (ORCID: https://orcid.org/0000-0002-9051-1896)
- Alain Fischer (ORCID: https://orcid.org/0000-0003-4025-5983)
- Juan Eduardo Montero-Hernández (ORCID: https://orcid.org/0000-0003-1158-6978)
- Céline Aoun
- Bernardita Medel (ORCID: https://orcid.org/0009-0006-9849-4214)
- Pablo Vargas (ORCID: https://orcid.org/0000-0002-6475-494X)
- Geneviève de Saint Basile (ORCID: https://orcid.org/0000-0002-1913-5269)
- Nicolas Goudin (ORCID: https://orcid.org/0000-0002-3967-4016)
- Brieuc P. Pérot (ORCID: https://orcid.org/0000-0002-4672-9943)
- Gaël Ménasché (ORCID: https://orcid.org/0000-0001-6671-3642)
- Fernando E. Sepulveda (ORCID: https://orcid.org/0000-0001-5865-4929)
- Mirjana Weimershaus (ORCID: https://orcid.org/0000-0003-2874-6608)
- Kerui Zhang
- Mathieu Kurowska (ORCID: https://orcid.org/0000-0003-0154-0079)
- Jian‐Dong Huang (ORCID: https://orcid.org/0000-0001-7531-2816)
- Mounia Debili
- Pierre Duquesne
- Linda Diedhiou
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Collège de France (FR)
- Université de Montpellier (FR)
- Université Paris Cité (FR)
- Institut Necker Enfants Malades (FR)
- Centre National pour la Recherche Scientifique et Technique (CNRST) (MA)
- Assistance Publique – Hôpitaux de Paris (FR)
- Comer Children's Hospital (US)
- Institut du Cerveau (FR)
- Institut de Génomique Fonctionnelle (FR)
- Institut des Maladies Génétiques Imagine (FR)
- NeuroDiderot (FR)
- University of Hong Kong (HK)
Publication Details
- Journal
- Science Advances
- Published
- 2025-10-17
- DOI
- https://doi.org/10.1126/sciadv.adx7672
- Citations
- 2
- Primary Topic
- Microtubule and mitosis dynamics
- Type
- article
- Field-Weighted Citation Impact
- 2.30
Funders
- Institut des maladies génétiques Imagine
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Fondation ARC pour la Recherche sur le Cancer
- Ligue Contre le Cancer
- Servier