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α-actinin-4 drives invasiveness by regulating myosin IIB expression and myosin IIA localization

Amlan Barai, Abhishek Mukherjee, Alakesh Das, Neha Saxena, View ORCID ProfileShamik Sen
doi: https://doi.org/10.1101/2021.01.12.426368
Amlan Barai
1Dept. of Biosciences & Bioengineering, IIT Bombay, Mumbai, India
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  • For correspondence: amlan.hp@gmail.com
Abhishek Mukherjee
2IITB-Monash Research Academy, Mumbai, India
3Dept. of Mechanical Engineering, IIT Bombay, Mumbai, India
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Alakesh Das
1Dept. of Biosciences & Bioengineering, IIT Bombay, Mumbai, India
4Dept. of Biological Regulation, Weizmann Institute of Science, Israel
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Neha Saxena
1Dept. of Biosciences & Bioengineering, IIT Bombay, Mumbai, India
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Shamik Sen
1Dept. of Biosciences & Bioengineering, IIT Bombay, Mumbai, India
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  • For correspondence: shamiks@iitb.ac.in
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Abstract

The mechanisms by which the mechanoresponsive actin crosslinking protein α-actinin-4 (ACTN4) regulates cell motility and invasiveness remains incompletely understood. Here we show that in addition to regulating protrusion dynamics and focal adhesion formation, ACTN4 transcriptionally regulates expression of non-muscle myosin IIB (NMM IIB), which is essential for mediating nuclear translocation during 3D invasion. We further demonstrate association between NMM IIA and ACTN4 at the cell front ensures retention of NMM IIA at the cell periphery. A protrusion-dependent model of confined migration recapitulating experimental observations predicts a dependence of protrusion forces on the degree of confinement and on the ratio of nucleus to matrix stiffness. Together, our results suggest that ACTN4 is a master regulator of cancer invasion that regulates invasiveness by controlling NMM IIB expression and NMM IIA localization.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted January 12, 2021.
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α-actinin-4 drives invasiveness by regulating myosin IIB expression and myosin IIA localization
Amlan Barai, Abhishek Mukherjee, Alakesh Das, Neha Saxena, Shamik Sen
bioRxiv 2021.01.12.426368; doi: https://doi.org/10.1101/2021.01.12.426368
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α-actinin-4 drives invasiveness by regulating myosin IIB expression and myosin IIA localization
Amlan Barai, Abhishek Mukherjee, Alakesh Das, Neha Saxena, Shamik Sen
bioRxiv 2021.01.12.426368; doi: https://doi.org/10.1101/2021.01.12.426368

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