Myosin II isoforms play distinct roles in adherens junction biogenesis
Abstract
Adherens junction (AJ) assembly under force is essential for many biological processes like epithelial monolayer bending, collective cell migration, cell extrusion and wound healing. The acto-myosin cytoskeleton acts as a major force-generator during the de novo formation and remodelling of AJ. Here, we investigated the role of myosinII isoforms in epithelial junction assembly. Myosin IIA (NMIIA) and Myosin IIB (NMIIB) differentially regulate biogenesis of adherens junction through association with distinct actin networks. Analysis of junction dynamics, actin organization, and mechanical forces of control and knockdown cells for myosins revealed that NMIIA provides the mechanical tugging force necessary for cell-cell junction reinforcement and maintenance. NMIIB is involved in E-cadherin clustering, maintenance of a branched actin layer connecting E-cadherin complexes and perijunctional actin fibres leading to the building-up of anisotropic stress. These data reveal unanticipated complementary functions of NMIIA and NMIIB in the biogenesis and integrity of AJ.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for the main figures and figure supplements.
Article and author information
Author details
Funding
Seventh Framework Programme (CoG-617233)
- Benoit Ladoux
Agence Nationale de la Recherche (ANR-17-CE13-0013)
- René-Marc Mège
Agence Nationale de la Recherche (ANR-10-INBS-04)
- René-Marc Mège
- Benoit Ladoux
Agence Nationale de la Recherche (ANR‐11‐LABX‐0071)
- René-Marc Mège
- Benoit Ladoux
Agence Nationale de la Recherche (ANR-11-LABX-0071)
- Benoit Ladoux
Agence Nationale de la Recherche (ANR-17-CE13-0012)
- Benoit Ladoux
Ligue Contre le Cancer (Equipe Labellisée)
- René-Marc Mège
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- William I Weis, Stanford University School of Medicine, United States
Version history
- Received: March 6, 2019
- Accepted: September 5, 2019
- Accepted Manuscript published: September 5, 2019 (version 1)
- Version of Record published: September 23, 2019 (version 2)
Copyright
© 2019, Heuze et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 4,723
- Page views
-
- 604
- Downloads
-
- 47
- Citations
Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Cell Biology
High-altitude polycythemia (HAPC) affects individuals living at high altitudes, characterized by increased red blood cells (RBCs) production in response to hypoxic conditions. The exact mechanisms behind HAPC are not fully understood. We utilized a mouse model exposed to hypobaric hypoxia (HH), replicating the environmental conditions experienced at 6000 m above sea level, coupled with in vitro analysis of primary splenic macrophages under 1% O2 to investigate these mechanisms. Our findings indicate that HH significantly boosts erythropoiesis, leading to erythrocytosis and splenic changes, including initial contraction to splenomegaly over 14 days. A notable decrease in red pulp macrophages (RPMs) in the spleen, essential for RBCs processing, was observed, correlating with increased iron release and signs of ferroptosis. Prolonged exposure to hypoxia further exacerbated these effects, mirrored in human peripheral blood mononuclear cells. Single-cell sequencing showed a marked reduction in macrophage populations, affecting the spleen’s ability to clear RBCs and contributing to splenomegaly. Our findings suggest splenic ferroptosis contributes to decreased RPMs, affecting erythrophagocytosis and potentially fostering continuous RBCs production in HAPC. These insights could guide the development of targeted therapies for HAPC, emphasizing the importance of splenic macrophages in disease pathology.
-
- Cell Biology
Mapping proteins in and associated with the Golgi apparatus reveals how this cellular compartment emerges in budding yeast and progresses over time.