Yosuke Senju, Toiba Mushtaq, Helena Vihinen, Aki Manninen, Juha Saarikangas, Katharina Ven, Ulrike Engel, Markku Varjosalo, Eija Jokitalo, Pekka Lappalainen, Actin-rich lamellipodia-like protrusions contribute to the integrity of epithelial cell–cell junctions, Journal of Biological Chemistry, Volume 299, Issue 5, 2023, 104571, ISSN 0021-9258, https://doi.org/10.1016/j.jbc.2023.104571
Actin-rich lamellipodia-like protrusions contribute to the integrity of epithelial cell–cell junctions
|Author:||Senju, Yosuke1,2; Mushtaq, Toiba1; Vihinen, Helena1;|
1Helsinki Institute of Life Science (HiLIFE) - Institute of Biotechnology, University of Helsinki, Helsinki, Finland
2Research Institute for Interdisciplinary Science (RIIS), Okayama University, Okayama, Japan
3Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Oulu, Finland
4Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland
5Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, Neuroscience Center, University of Helsinki, Helsinki, Finland
6Nikon Imaging Center and Centre for Organismal Studies, Heidelberg University, Heidelberg, Germany
|Online Access:||PDF Full Text (PDF, 5.7 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe20230927137634
American Society for Biochemistry and Molecular Biology,
|Publish Date:|| 2023-09-27
Metastasis-suppressor 1 (MTSS1) is a membrane-interacting scaffolding protein that regulates the integrity of epithelial cell–cell junctions and functions as a tumor suppressor in a wide range of carcinomas. MTSS1 binds phosphoinositide-rich membranes through its I-BAR domain and is capable of sensing and generating negative membrane curvature in vitro. However, the mechanisms by which MTSS1 localizes to intercellular junctions in epithelial cells and contributes to their integrity and maintenance have remained elusive. By carrying out EM and live-cell imaging on cultured Madin-Darby canine kidney cell monolayers, we provide evidence that adherens junctions of epithelial cells harbor lamellipodia-like, dynamic actin-driven membrane folds, which exhibit high negative membrane curvature at their distal edges. BioID proteomics and imaging experiments demonstrated that MTSS1 associates with an Arp2/3 complex activator, the WAVE-2 complex, in dynamic actin-rich protrusions at cell–cell junctions. Inhibition of Arp2/3 or WAVE-2 suppressed actin filament assembly at adherens junctions, decreased the dynamics of junctional membrane protrusions, and led to defects in epithelial integrity. Together, these results support a model in which membrane-associated MTSS1, together with the WAVE-2 and Arp2/3 complexes, promotes the formation of dynamic lamellipodia-like actin protrusions that contribute to the integrity of cell–cell junctions in epithelial monolayers.
Journal of biological chemistry
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
1182 Biochemistry, cell and molecular biology
This study was supported by the FY 2015 Researcher Exchange Program between the Japan Society for the Promotion of Science (JSPS) and Academy of Finland (AF) (Y. S.), Astellas Foundation for Research on Metabolic Disorders (Y. S.), the Scandinavia-Japan Sasakawa Foundation (Y. S.), the Ichiro Kanehara Foundation for the Promotion of Medical Sciences and Medical Care (Y. S.), The Association for Fordays Self-Reliance Support in Japan (Y. S.), Okayama Foundation for Science and Technology (Y. S.), ONO Medical Research Foundation (Y. S.), Takeda Science Foundation (Y. S.), The Naito Foundation (Y. S.), The Company of Biologists (Y. S.), European Biophysical Societies Association (EBSA) (Y. S.), Human Frontier Science Program (P. L.), and Cancer Society Finland (P. L.).
© 2023 THE AUTHORS. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).