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Mechanical strain stimulates COPII-dependent trafficking via Rac1

Santosh Phuyal, Elena Djaerff, View ORCID ProfileAnabel-Lise Le Roux, Martin J. Baker, Daniela Fankhauser, Sayyed Jalil Mahdizadeh, Veronika Reiterer, Jennifer C. Kahlhofer, View ORCID ProfileDavid Teis, View ORCID ProfileMarcelo G. Kazanietz, View ORCID ProfileStephan Geley, Leif Eriksson, Pere Roca-Cusachs, Hesso Farhan
doi: https://doi.org/10.1101/2022.01.23.477215
Santosh Phuyal
1Institute of Basic Medical Sciences, University of Oslo, Norway
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  • For correspondence: santosh.phuyal@medisin.uio.no proca@ibecbarcelona.eu hesso.farhan@i-med.ac.at
Elena Djaerff
1Institute of Basic Medical Sciences, University of Oslo, Norway
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Anabel-Lise Le Roux
2Institute for Bioengineering of Catalonia (IBEC), the Barcelona Institute of Technology (BIST), 08028 Barcelona, Spain
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  • ORCID record for Anabel-Lise Le Roux
Martin J. Baker
3Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
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Daniela Fankhauser
4Institute of Pathophysiology, Medical University of Innsbruck, Austria
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Sayyed Jalil Mahdizadeh
5Department of chemistry and molecular biology, University of Gothenburg, Sweden
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Veronika Reiterer
4Institute of Pathophysiology, Medical University of Innsbruck, Austria
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Jennifer C. Kahlhofer
6Institute of Cell Biology, Medical University of Innsbruck, Austria
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David Teis
6Institute of Cell Biology, Medical University of Innsbruck, Austria
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Marcelo G. Kazanietz
3Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
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  • ORCID record for Marcelo G. Kazanietz
Stephan Geley
4Institute of Pathophysiology, Medical University of Innsbruck, Austria
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Leif Eriksson
5Department of chemistry and molecular biology, University of Gothenburg, Sweden
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Pere Roca-Cusachs
2Institute for Bioengineering of Catalonia (IBEC), the Barcelona Institute of Technology (BIST), 08028 Barcelona, Spain
7Universitat de Barcelona, 08036 Barcelona, Spain
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  • For correspondence: santosh.phuyal@medisin.uio.no proca@ibecbarcelona.eu hesso.farhan@i-med.ac.at
Hesso Farhan
1Institute of Basic Medical Sciences, University of Oslo, Norway
4Institute of Pathophysiology, Medical University of Innsbruck, Austria
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  • For correspondence: santosh.phuyal@medisin.uio.no proca@ibecbarcelona.eu hesso.farhan@i-med.ac.at
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Abstract

Secretory trafficking from the endoplasmic reticulum (ER) is subject to regulation by extrinsic and intrinsic factors. While much of the focus has been on biochemical triggers, little is known whether and how the ER is subject to regulation by mechanical signals. Here, we show that COPII-dependent ER-export is regulated by mechanical strain. Mechanotransduction to the ER was mediated via a previously unappreciated ER-localized pool of the small GTPase Rac1. Mechanistically, we show that Rac1 interacts with the small GTPase Sar1 to drive budding of COPII carriers and stimulate ER-to-Golgi transport. Altogether, we establish an unprecedented link between mechanical strain and export from the ER.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
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 23, 2022.
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Mechanical strain stimulates COPII-dependent trafficking via Rac1
Santosh Phuyal, Elena Djaerff, Anabel-Lise Le Roux, Martin J. Baker, Daniela Fankhauser, Sayyed Jalil Mahdizadeh, Veronika Reiterer, Jennifer C. Kahlhofer, David Teis, Marcelo G. Kazanietz, Stephan Geley, Leif Eriksson, Pere Roca-Cusachs, Hesso Farhan
bioRxiv 2022.01.23.477215; doi: https://doi.org/10.1101/2022.01.23.477215
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Mechanical strain stimulates COPII-dependent trafficking via Rac1
Santosh Phuyal, Elena Djaerff, Anabel-Lise Le Roux, Martin J. Baker, Daniela Fankhauser, Sayyed Jalil Mahdizadeh, Veronika Reiterer, Jennifer C. Kahlhofer, David Teis, Marcelo G. Kazanietz, Stephan Geley, Leif Eriksson, Pere Roca-Cusachs, Hesso Farhan
bioRxiv 2022.01.23.477215; doi: https://doi.org/10.1101/2022.01.23.477215

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