Fascin limits Myosin activity within Drosophila border cells to control substrate stiffness and promote migration

Maureen C Lamb; Chathuri P Kaluarachchi; Thiranjeewa I Lansakara; Samuel Q Mellentine; Yiling Lan; Alexei V Tivanski; Tina L Tootle

doi:10.7554/eLife.69836

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Fascin limits Myosin activity within Drosophila border cells to control substrate stiffness and promote migration

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Fascin limits Myosin activity within Drosophila border cells to control substrate stiffness and promote migration

Maureen C Lamb, Chathuri P Kaluarachchi, Thiranjeewa I Lansakara, Samuel Q Mellentine, Yiling Lan, Alexei V Tivanski and Tina L Tootle

eLife, Vol.10, e69836

10/26/2021

DOI: 10.7554/eLife.69836

PMCID: PMC8547955

PMID: 34698017

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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 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 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.

Animals

Carrier Proteins - genetics

Carrier Proteins - metabolism

Cell Movement - physiology

Drosophila melanogaster - genetics

Drosophila melanogaster - physiology

Microfilament Proteins - genetics

Microfilament Proteins - metabolism

Myosins - metabolism

Details

Title: Subtitle: Fascin limits Myosin activity within Drosophila border cells to control substrate stiffness and promote migration
Creators: Maureen C Lamb - Anatomy and Cell Biology, University of Iowa Carver College of Medicine, Iowa City, United States
Chathuri P Kaluarachchi - Department of Chemistry, University of Iowa, Iowa City, United States
Thiranjeewa I Lansakara - Department of Chemistry, University of Iowa, Iowa City, United States
Samuel Q Mellentine - Anatomy and Cell Biology, University of Iowa Carver College of Medicine, Iowa City, United States
Yiling Lan - Department of Chemistry, University of Iowa, Iowa City, United States
Alexei V Tivanski - Department of Chemistry, University of Iowa, Iowa City, United States
Tina L Tootle - Anatomy and Cell Biology, University of Iowa Carver College of Medicine, Iowa City, United States
Resource Type: Journal article
Publication Details: eLife, Vol.10, e69836
DOI: 10.7554/eLife.69836
PMID: 34698017
PMCID: PMC8547955
NLM abbreviation: Elife
ISSN: 2050-084X
eISSN: 2050-084X
Grant note: R01 GM116885 / NIGMS NIH HHS P40 OD018537 / NIH HHS P30 CA086862 / NCI NIH HHS
Language: English
Date published: 10/26/2021
Academic Unit: Anatomy and Cell Biology; Biology; Chemistry
Record Identifier: 9984216615602771

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