Stochastic activation and bistability in a Rab GTPase regulatory network

U. Bezeljak, H. Loya, B.M. Kaczmarek, T.E. Saunders, M. Loose, Proceedings of the National Academy of Sciences 117 (2020) 6504–6549.


Journal Article | Published | English
Author
Abstract
The eukaryotic endomembrane system is controlled by small GTPases of the Rab family, which are activated at defined times and locations in a switch-like manner. While this switch is well understood for an individual protein, how regulatory networks produce intracellular activity patterns is currently not known. Here, we combine in vitro reconstitution experiments with computational modeling to study a minimal Rab5 activation network. We find that the molecular interactions in this system give rise to a positive feedback and bistable collective switching of Rab5. Furthermore, we find that switching near the critical point is intrinsically stochastic and provide evidence that controlling the inactive population of Rab5 on the membrane can shape the network response. Notably, we demonstrate that collective switching can spread on the membrane surface as a traveling wave of Rab5 activation. Together, our findings reveal how biochemical signaling networks control vesicle trafficking pathways and how their nonequilibrium properties define the spatiotemporal organization of the cell.
Publishing Year
Date Published
2020-03-24
Journal Title
Proceedings of the National Academy of Sciences
Volume
117
Issue
12
Page
6504-6549
IST-REx-ID

Cite this

Bezeljak U, Loya H, Kaczmarek BM, Saunders TE, Loose M. Stochastic activation and bistability in a Rab GTPase regulatory network. Proceedings of the National Academy of Sciences. 2020;117(12):6504-6549. doi:10.1073/pnas.1921027117
Bezeljak, U., Loya, H., Kaczmarek, B. M., Saunders, T. E., & Loose, M. (2020). Stochastic activation and bistability in a Rab GTPase regulatory network. Proceedings of the National Academy of Sciences, 117(12), 6504–6549. https://doi.org/10.1073/pnas.1921027117
Bezeljak, Urban, Hrushikesh Loya, Beata M Kaczmarek, Timothy E. Saunders, and Martin Loose. “Stochastic Activation and Bistability in a Rab GTPase Regulatory Network.” Proceedings of the National Academy of Sciences 117, no. 12 (2020): 6504–49. https://doi.org/10.1073/pnas.1921027117.
U. Bezeljak, H. Loya, B. M. Kaczmarek, T. E. Saunders, and M. Loose, “Stochastic activation and bistability in a Rab GTPase regulatory network,” Proceedings of the National Academy of Sciences, vol. 117, no. 12, pp. 6504–6549, 2020.
Bezeljak U, Loya H, Kaczmarek BM, Saunders TE, Loose M. 2020. Stochastic activation and bistability in a Rab GTPase regulatory network. Proceedings of the National Academy of Sciences. 117(12), 6504–6549.
Bezeljak, Urban, et al. “Stochastic Activation and Bistability in a Rab GTPase Regulatory Network.” Proceedings of the National Academy of Sciences, vol. 117, no. 12, Proceedings of the National Academy of Sciences, 2020, pp. 6504–49, doi:10.1073/pnas.1921027117.

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