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Membrane-proximal F-actin restricts local membrane protrusions and directs cell migration
Anjali Bisaria1, Arnold Hayer2, Damien Garbett2
1Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA, USA. abisaria@stanford.edu tom4003@med.cornell.edu.
Science (New York, N.Y.)
|June 13, 2020
Summary
Membrane-proximal actin (MPA) density, not total actin, directs cell protrusion. Low MPA at the cell front drives membrane extension, stabilizing cell migration and polarization.
Area of Science:
- Cell Biology
- Biophysics
- Molecular Motors
Background:
- Cell migration relies on actin polymerization for membrane protrusion.
- Membrane-proximal actin (MPA) can impede protrusion by tethering the cell membrane.
Purpose of the Study:
- To develop a method for visualizing and quantifying MPA dynamics during cell migration.
- To investigate the role of MPA density gradients in directing membrane protrusions and cell polarization.
Main Methods:
- Development of a novel fluorescent reporter for membrane-proximal F-actin (MPA).
- Live-cell imaging to monitor MPA density changes during cell migration.
- Analysis of F-actin turnover rates and their correlation with MPA distribution.
Main Results:
- MPA density was found to be low at the leading edge and high at the rear of migrating cells.
- A back-to-front gradient in MPA density was established by increased F-actin turnover at the front, regulated by cofilin.
- New membrane protrusions initiated specifically from regions with reduced MPA density.
Conclusions:
- Locally decreased MPA density is a key regulator of directed membrane protrusion during cell migration.
- MPA density gradients play a critical role in stabilizing cell polarity and directing migration.
- This study reveals a novel mechanism controlling cell movement at the molecular level.
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