Fascin limits Myosin activity within Drosophila border cells to control substrate stiffness and promote migration
- University of Iowa Carver College of Medicine, United States
- University of Iowa, United States
Abstract
A key regulator of collective cell migrations, which drive development and cancer metastasis, is substrate stiffness. Increased substrate stiffness promotes migration and is controlled by Myosin. Using Drosophila border cell migration as a model of collective cell migration, we identify, for the first time, that the actin bundling protein Fascin limits Myosin activity in vivo. Loss of Fascin results in: increased activated Myosin on the border cells and their substrate, the nurse cells; decreased border cell Myosin dynamics; and increased nurse cell stiffness as measured by atomic force microscopy. Reducing Myosin restores on-time border cell migration in fascin mutant follicles. Further, Fascin’s actin bundling activity is required to limit Myosin activation. Surprisingly, we find that Fascin regulates Myosin activity in the border cells to control nurse cell stiffness to promote migration. Thus, these data shift the paradigm from a substrate stiffness-centric model of regulating migration, to uncover that collectively migrating cells play a critical role in controlling the mechanical properties of their substrate in order to promote their own migration. This understudied means of mechanical regulation of migration is likely conserved across contexts and organisms, as Fascin and Myosin are common regulators of cell migration.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting file 1.
Article and author information
Author details
Chathuri P Kaluarachchi
Funding
National Institute of General Medical Sciences (R01GM116885)
- Maureen C Lamb
- Samuel Q Mellentine
- Tina L Tootle
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2021, Lamb 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.
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Fascin limits Myosin activity within Drosophila border cells to control substrate stiffness and promote migration
eLife 10:e69836.
https://doi.org/10.7554/eLife.69836
