Focal adhesions are controlled by microtubules through local contractility regulation

Julien Aureille; Srinivas S. Prabhu; Sam F. Barnett; Aaron J. Farrugia; Isabelle Arnal; Laurence Lafanechère; Boon Chuan Low; Pakorn Kanchanawong; Alex Mogilner; Alexander D. Bershadsky

doi:10.1038/s44318-024-00114-4

Focal adhesions are controlled by microtubules through local contractility regulation

Julien Aureille^*, Srinivas S. Prabhu, Sam F. Barnett, Aaron J. Farrugia, Isabelle Arnal, Laurence Lafanechère, Boon Chuan Low, Pakorn Kanchanawong, Alex Mogilner, Alexander D. Bershadsky^*

^*Corresponding author for this work

Department of Molecular Cell Biology

Research output: Contribution to journal › Article › peer-review

Abstract

(Figure presented.) Progressive microtubule capture during focal adhesion maturation ultimately triggers focal adhesion turnover. This study shows that local development of actomyosin traction force induces focal adhesion sliding, thus mediating focal adhesion disassembly upon interaction with microtubules. An optogenetic construct of KANK1 protein enables targeting of microtubules to focal adhesions upon local blue light illumination. Illumination-induced increase in the number of microtubule tips at focal adhesion is followed by their withdrawal, and by accumulation of myosin-II filaments. Local transient development of traction force is followed by focal adhesion sliding and disassembly. Disassembly of focal adhesion induced by OptoKANK-driven microtubule targeting depends on Rho activation by the microtubule-associated GEF-H1 and other factors. A mathematical model replicates the observed microtubule-driven focal adhesion disassembly due to myosin-II mediated traction force generation.

Original language	English
Pages (from-to)	2715-2732
Number of pages	18
Journal	EMBO Journal
Volume	43
Issue number	13
DOIs	https://doi.org/10.1038/s44318-024-00114-4
Publication status	Published Online - 20 May 2024

Bibliographical note

We thank Christophe Guilluy for support and encouragements, A. Wong (MBI, Singapore) for expert help in paper editing, Bryant L. Doss for advices with the TFM experiments, Yukako Nishimura (Hokkaido University) for advices with the MY-134 pillars technology, M. Davidson fluorescence protein collection (The Florida State University, Tallahassee, USA), the SIMBA microscopy facility, the Wet Lab and nanofabrication core facility at the Mechanobiology Institute for technical help. The research is supported in part by the National Research Foundation, Prime Minister’s Office, Singapore, Singapore Ministry of Education under the Research Centres of Excellence program through the Mechanobiology Institute at the National University of Singapore (refs no. R-714-006-006-271, A-0003467-01-00 and A-0003467-00-00), by the National Research Foundation Singapore under its Mid-Sized Grant (NRF-MSG-2023-0001-0003), by the Singapore Ministry of Education Academic Research Fund Tier 2 (MOE Grant No: MOE2018-T2-2-138, awarded to ADB; MOE2019-T2-1-099 and MOE2019-T2-02-014; awarded to PK), and Tier 3 (MOE Grant No: MOE2016-T3-1-002 and MOET32021-0003; awarded to BC and ADB), as well as by Neurodis Foundation (awarded to JA, ref R2311CC), and by US National Science Foundation (DMS1953430, awarded to AM).

Publisher Copyright:
© The Author(s) 2024.

All Science Journal Classification (ASJC) codes

General Neuroscience
Molecular Biology
General Biochemistry,Genetics and Molecular Biology
General Immunology and Microbiology

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10.1038/s44318-024-00114-4Licence: CC BY

Cite this

@article{68421ea247ca40a49c05e18b07b9bee0,

title = "Focal adhesions are controlled by microtubules through local contractility regulation",

abstract = "(Figure presented.) Progressive microtubule capture during focal adhesion maturation ultimately triggers focal adhesion turnover. This study shows that local development of actomyosin traction force induces focal adhesion sliding, thus mediating focal adhesion disassembly upon interaction with microtubules. An optogenetic construct of KANK1 protein enables targeting of microtubules to focal adhesions upon local blue light illumination. Illumination-induced increase in the number of microtubule tips at focal adhesion is followed by their withdrawal, and by accumulation of myosin-II filaments. Local transient development of traction force is followed by focal adhesion sliding and disassembly. Disassembly of focal adhesion induced by OptoKANK-driven microtubule targeting depends on Rho activation by the microtubule-associated GEF-H1 and other factors. A mathematical model replicates the observed microtubule-driven focal adhesion disassembly due to myosin-II mediated traction force generation.",

author = "Julien Aureille and Prabhu, {Srinivas S.} and Barnett, {Sam F.} and Farrugia, {Aaron J.} and Isabelle Arnal and Laurence Lafanech{\`e}re and Low, {Boon Chuan} and Pakorn Kanchanawong and Alex Mogilner and Bershadsky, {Alexander D.}",

note = "We thank Christophe Guilluy for support and encouragements, A. Wong (MBI, Singapore) for expert help in paper editing, Bryant L. Doss for advices with the TFM experiments, Yukako Nishimura (Hokkaido University) for advices with the MY-134 pillars technology, M. Davidson fluorescence protein collection (The Florida State University, Tallahassee, USA), the SIMBA microscopy facility, the Wet Lab and nanofabrication core facility at the Mechanobiology Institute for technical help. The research is supported in part by the National Research Foundation, Prime Minister{\textquoteright}s Office, Singapore, Singapore Ministry of Education under the Research Centres of Excellence program through the Mechanobiology Institute at the National University of Singapore (refs no. R-714-006-006-271, A-0003467-01-00 and A-0003467-00-00), by the National Research Foundation Singapore under its Mid-Sized Grant (NRF-MSG-2023-0001-0003), by the Singapore Ministry of Education Academic Research Fund Tier 2 (MOE Grant No: MOE2018-T2-2-138, awarded to ADB; MOE2019-T2-1-099 and MOE2019-T2-02-014; awarded to PK), and Tier 3 (MOE Grant No: MOE2016-T3-1-002 and MOET32021-0003; awarded to BC and ADB), as well as by Neurodis Foundation (awarded to JA, ref R2311CC), and by US National Science Foundation (DMS1953430, awarded to AM). Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

month = may,

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doi = "10.1038/s44318-024-00114-4",

language = "English",

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T1 - Focal adhesions are controlled by microtubules through local contractility regulation

AU - Aureille, Julien

AU - Prabhu, Srinivas S.

AU - Barnett, Sam F.

AU - Farrugia, Aaron J.

AU - Arnal, Isabelle

AU - Lafanechère, Laurence

AU - Low, Boon Chuan

AU - Kanchanawong, Pakorn

AU - Mogilner, Alex

AU - Bershadsky, Alexander D.

N1 - We thank Christophe Guilluy for support and encouragements, A. Wong (MBI, Singapore) for expert help in paper editing, Bryant L. Doss for advices with the TFM experiments, Yukako Nishimura (Hokkaido University) for advices with the MY-134 pillars technology, M. Davidson fluorescence protein collection (The Florida State University, Tallahassee, USA), the SIMBA microscopy facility, the Wet Lab and nanofabrication core facility at the Mechanobiology Institute for technical help. The research is supported in part by the National Research Foundation, Prime Minister’s Office, Singapore, Singapore Ministry of Education under the Research Centres of Excellence program through the Mechanobiology Institute at the National University of Singapore (refs no. R-714-006-006-271, A-0003467-01-00 and A-0003467-00-00), by the National Research Foundation Singapore under its Mid-Sized Grant (NRF-MSG-2023-0001-0003), by the Singapore Ministry of Education Academic Research Fund Tier 2 (MOE Grant No: MOE2018-T2-2-138, awarded to ADB; MOE2019-T2-1-099 and MOE2019-T2-02-014; awarded to PK), and Tier 3 (MOE Grant No: MOE2016-T3-1-002 and MOET32021-0003; awarded to BC and ADB), as well as by Neurodis Foundation (awarded to JA, ref R2311CC), and by US National Science Foundation (DMS1953430, awarded to AM). Publisher Copyright: © The Author(s) 2024.

PY - 2024/5/20

Y1 - 2024/5/20

N2 - (Figure presented.) Progressive microtubule capture during focal adhesion maturation ultimately triggers focal adhesion turnover. This study shows that local development of actomyosin traction force induces focal adhesion sliding, thus mediating focal adhesion disassembly upon interaction with microtubules. An optogenetic construct of KANK1 protein enables targeting of microtubules to focal adhesions upon local blue light illumination. Illumination-induced increase in the number of microtubule tips at focal adhesion is followed by their withdrawal, and by accumulation of myosin-II filaments. Local transient development of traction force is followed by focal adhesion sliding and disassembly. Disassembly of focal adhesion induced by OptoKANK-driven microtubule targeting depends on Rho activation by the microtubule-associated GEF-H1 and other factors. A mathematical model replicates the observed microtubule-driven focal adhesion disassembly due to myosin-II mediated traction force generation.

AB - (Figure presented.) Progressive microtubule capture during focal adhesion maturation ultimately triggers focal adhesion turnover. This study shows that local development of actomyosin traction force induces focal adhesion sliding, thus mediating focal adhesion disassembly upon interaction with microtubules. An optogenetic construct of KANK1 protein enables targeting of microtubules to focal adhesions upon local blue light illumination. Illumination-induced increase in the number of microtubule tips at focal adhesion is followed by their withdrawal, and by accumulation of myosin-II filaments. Local transient development of traction force is followed by focal adhesion sliding and disassembly. Disassembly of focal adhesion induced by OptoKANK-driven microtubule targeting depends on Rho activation by the microtubule-associated GEF-H1 and other factors. A mathematical model replicates the observed microtubule-driven focal adhesion disassembly due to myosin-II mediated traction force generation.

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U2 - 10.1038/s44318-024-00114-4

DO - 10.1038/s44318-024-00114-4

M3 - Article

AN - SCOPUS:85193588037

SN - 0261-4189

VL - 43

SP - 2715

EP - 2732

JO - EMBO Journal

JF - EMBO Journal

IS - 13

ER -

Focal adhesions are controlled by microtubules through local contractility regulation

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

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