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Stochastic activation and bistability in a Rab GTPase regulatory network

View ORCID ProfileUrban Bezeljak, Hrushikesh Loya, Beata Kaczmarek, Timothy E. Saunders, View ORCID ProfileMartin Loose
doi: https://doi.org/10.1101/776567
Urban Bezeljak
1Institute for Science and Technology Austria (IST Austria), Klosterneuburg, Austria
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  • ORCID record for Urban Bezeljak
Hrushikesh Loya
2Indian Institute of Technology, Bombay, India
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Beata Kaczmarek
1Institute for Science and Technology Austria (IST Austria), Klosterneuburg, Austria
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Timothy E. Saunders
3Mechanobiology Institute and Department of Biological Sciences, National University of Singapore, Singapore
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  • For correspondence: martin.loose@ist.ac.at dbsste@nus.edu.sg
Martin Loose
1Institute for Science and Technology Austria (IST Austria), Klosterneuburg, Austria
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  • ORCID record for Martin Loose
  • For correspondence: martin.loose@ist.ac.at dbsste@nus.edu.sg
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Abstract

Rab GTPases are the central regulators of intracellular traffic. Their function relies on a conformational change triggered by nucleotide exchange and hydrolysis. While this switch is well understood for an individual protein, how Rab GTPases collectively transition between states to generate a biochemical signal in space and time is unclear. Here, we combine in vitro reconstitution experiments with theoretical modeling to study a minimal Rab5 activation network. We find that positive feedback in this network gives rise to bistable switching of Rab5 activation and provide evidence that controlling the inactive population of Rab5 on the membrane can shape the network response. Together, our findings reveal new insights into the non-equilibrium properties and general principles of biochemical signaling networks underlying the spatiotemporal organization of the cell.

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Posted September 23, 2019.
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Stochastic activation and bistability in a Rab GTPase regulatory network
Urban Bezeljak, Hrushikesh Loya, Beata Kaczmarek, Timothy E. Saunders, Martin Loose
bioRxiv 776567; doi: https://doi.org/10.1101/776567
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Stochastic activation and bistability in a Rab GTPase regulatory network
Urban Bezeljak, Hrushikesh Loya, Beata Kaczmarek, Timothy E. Saunders, Martin Loose
bioRxiv 776567; doi: https://doi.org/10.1101/776567

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