Myosins 1e/f at the podosome base regulate podosome dynamics and promote macrophage migration

Sep 29, 2026

Uploaded by jayni

Monocyte-lineage cells form podosomes, specialized actin-rich membrane-associated structures that support adhesion, migration, and extracellular matrix degradation. This study identifies class I myosins, Myo1e and Myo1f, as podosome-localized proteins concentrated beneath the podosome core near the ventral plasma membrane, with localization driven mainly by Myo1e/f TH2 domains. Knockdowns or knockouts enlarge podosomes, alter turnover and lateral mobility, and reduce efficient linking of core actin filaments to the plasma membrane, while Myo1e/f double knockout macrophages show impaired migration despite enhanced matrix degradation.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages26

Reading Time1 h 6 min

AccessFree to download

Abstract

Keywords

Introduction

Author Manuscr ipt Author Manuscr ipt Author Manuscr ipt Author Manuscript | | HHS Public Access
Author manuscript
Eur J Cell Biol. Author manuscript; available in PMC 2026 January 06. | | --- | --- | Published in final edited form as: Eur J Cell Biol. 2025 December ; 104(4): 151514. doi:10.1016/j.ejcb.2025.151514 . Myosins 1e/f at the podosome base regulate podosome dynamics and promote macrophage migration Pasquale Cerveroa,1 , Sarah R. Bargerb,1,3 , Perrine Verdysc, Robert Herzoga, Tyler Paulb, Renaud Poinclouxc, Stefan Lindera,* , Mira Krendelb,* aInstitut für medizinische Mikrobiologie, Virologie und Hygiene, Universitätsklinikum Eppendorf, Martinistr. 52, Hamburg 20246, Germany bSUNY Upstate Medical University, 750 E Adams St. , Syracuse, NY 13210, USA c Institut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, CNRS UMR 5089, UPS, Toulouse, France Abstract Cells of the monocyte lineage form specialized membrane-associated, actin-rich structures, called podosomes. Podosomes play important roles in cell adhesion and migration as well as the proteolytic degradation of the extracellular matrix. While podosomes are always closely associated with the plasma membrane, the structural components linking the podosome core, composed of branched actin, to the membrane are not fully understood. In this study we show that class Imyosins, Myo1e and Myo1f, localize to a specific region of podosomes, underneath the podosome core and near the ventral plasma membrane, and that this localization is mainly mediated by the Myo1e/f TH2 domains. Respective knockdowns or knockouts of Myo1e/f lead to increased podosome size, altered turnover and lateral mobility, which is likely due to Myo1e/fregulating the attachment of core actin filaments to the plasma membrane. In addition, Myo1e/fdouble knockout macrophages were characterized by a reduction in 3D and 2D migration, even though these cells exhibited increased ability to degrade the extracellular matrix. Along with the other membraneassociated podosome components, such as the transmembrane protein MT-MMP and the GPIanchored DNase X, Myo1e and Myo1f mark the membrane-proximal region of podosomes. We This is an open access article under the CC BY-NC license ([http://creativecommons.org/licenses/by-nc/4.0/](http://creativecommons.org/licenses/by-nc/4.0/)). CEorresqualpconding aontributithnors. s.linder@uke.de (S. Linder), [krendelm@upstate.edu](krendelm@upstate.edu) (M. Krendel). 3Current address: Department of Molecular, Cellular, Developmental Biology, Yale University, 266 Whitney Ave., New Haven, CT 06511, USA. CRediT authorship contribution statement Pasquale Cervero: Writing – review & editing, Writing – original draft, Visualization, Validation, Methodology, Investigation, Formal analysis, Data curation, Conceptualization. Sarah R. Barger: Writing – review & editing, Writing – original draft, Visualization, Validation, Methodology, Investigation, Formal analysis, Data curation, Conceptualization. Perrine Verdys: Writing – review & editing, Visualization, Methodology, Investigation, Formal analysis. Robert Herzog: Software, Formal analysis. Tyler Paul: Investigation, Formal analysis. Renaud Poincloux: Writing – review & editing, Methodology, Conceptualization. Stefan Linder: Writing – review & editing, Writing – original draft, Supervision, Project administration, Methodology, Investigation, Funding acquisition, Conceptualization. Mira Krendel: Writing – review & editing, Writing – original draft, Visualization, Supervision, Resources, Project administration, Methodology, Investigation, Funding acquisition, Conceptualization. Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Author Manuscr ipt Author Manuscr ipt Author Manuscr ipt Author Manuscript Cervero et al. Page 2

FAQs

What are podosomes and what roles do they play in macrophages?

Podosomes are specialized actin-rich, membrane-associated adhesion structures. They support cell adhesion and migration and also enable proteolytic degradation of the extracellular matrix.

How do Myo1e and Myo1f relate to the podosome structure?

Myo1e and Myo1f localize to a specific region of podosomes beneath the core and near the ventral plasma membrane. Their localization is mainly mediated by the Myo1e/f TH2 domains.

What changes occur when Myo1e/f are knocked down or knocked out?

Loss of Myo1e/f increases podosome size and changes turnover and lateral mobility. Double knockout macrophages show reduced 3D and 2D migration while exhibiting increased capacity to degrade the extracellular matrix.

Sep 29, 2026

Uploaded by jayni