Atypical cofilin signaling drives dendritic cell migration through the extracellular matrix via nuclear deformation

Harry Warner; Giulia Franciosa; Guus van der Borg; Britt Coenen; Felix Faas; Claire Koenig; Rinse de Boer; René Classens; Sjors Maassen; Maksim V. Baranov; Shweta Mahajan; Deepti Dabral; Frans Bianchi; Niek van Hilten; Herre Jelger Risselada; Wouter H. Roos; Jesper Velgaard Olsen; Laia Querol Cano; Geert van den Bogaart

Cell Reports (Mar 2024)

Atypical cofilin signaling drives dendritic cell migration through the extracellular matrix via nuclear deformation

Harry Warner,
Giulia Franciosa,
Guus van der Borg,
Britt Coenen,
Felix Faas,
Claire Koenig,
Rinse de Boer,
René Classens,
Sjors Maassen,
Maksim V. Baranov,
Shweta Mahajan,
Deepti Dabral,
Frans Bianchi,
Niek van Hilten,
Herre Jelger Risselada,
Wouter H. Roos,
Jesper Velgaard Olsen,
Laia Querol Cano,
Geert van den Bogaart

Affiliations

Harry Warner: Department of Molecular Immunology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, the Netherlands
Giulia Franciosa: Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Guus van der Borg: Molecular Biophysics, Zernike Institute for Advanced Materials, University of Groningen, Groningen, the Netherlands
Britt Coenen: Department of Molecular Immunology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, the Netherlands
Felix Faas: Department of Molecular Immunology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, the Netherlands
Claire Koenig: Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Rinse de Boer: Department of Molecular Immunology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, the Netherlands
René Classens: Department of Tumour Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands
Sjors Maassen: Department of Molecular Immunology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, the Netherlands
Maksim V. Baranov: Department of Molecular Immunology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, the Netherlands
Shweta Mahajan: Department of Molecular Immunology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, the Netherlands
Deepti Dabral: Department of Molecular Immunology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, the Netherlands
Frans Bianchi: Department of Molecular Immunology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, the Netherlands
Niek van Hilten: Leiden Institute of Chemistry, Leiden University, Leiden, the Netherlands
Herre Jelger Risselada: Leiden Institute of Chemistry, Leiden University, Leiden, the Netherlands; Department of Physics, TU Dortmund, Dortmund, Germany
Wouter H. Roos: Molecular Biophysics, Zernike Institute for Advanced Materials, University of Groningen, Groningen, the Netherlands
Jesper Velgaard Olsen: Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Laia Querol Cano: Department of Tumour Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands
Geert van den Bogaart: Department of Molecular Immunology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, the Netherlands; Department of Pathology and Medical Biology, University Medical Center Groningen, Groningen, the Netherlands; Corresponding author

Journal volume & issue: Vol. 43, no. 3
p. 113866

Abstract

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Summary: To mount an adaptive immune response, dendritic cells must migrate to lymph nodes to present antigens to T cells. Critical to 3D migration is the nucleus, which is the size-limiting barrier for migration through the extracellular matrix. Here, we show that inflammatory activation of dendritic cells leads to the nucleus becoming spherically deformed and enables dendritic cells to overcome the typical 2- to 3-μm diameter limit for 3D migration through gaps in the extracellular matrix. We show that the nuclear shape change is partially attained through reduced cell adhesion, whereas improved 3D migration is achieved through reprogramming of the actin cytoskeleton. Specifically, our data point to a model whereby the phosphorylation of cofilin-1 at serine 41 drives the assembly of a cofilin-actomyosin ring proximal to the nucleus and enhances migration through 3D collagen gels. In summary, these data describe signaling events through which dendritic cells deform their nucleus and enhance their migratory capacity.

CP: Cell biology

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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