---
_id: '7580'
abstract:
- lang: eng
  text: 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.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
article_processing_charge: No
article_type: original
author:
- first_name: Urban
  full_name: Bezeljak, Urban
  id: 2A58201A-F248-11E8-B48F-1D18A9856A87
  last_name: Bezeljak
  orcid: 0000-0003-1365-5631
- first_name: Hrushikesh
  full_name: Loya, Hrushikesh
  last_name: Loya
- first_name: Beata M
  full_name: Kaczmarek, Beata M
  id: 36FA4AFA-F248-11E8-B48F-1D18A9856A87
  last_name: Kaczmarek
- first_name: Timothy E.
  full_name: Saunders, Timothy E.
  last_name: Saunders
- first_name: Martin
  full_name: Loose, Martin
  id: 462D4284-F248-11E8-B48F-1D18A9856A87
  last_name: Loose
  orcid: 0000-0001-7309-9724
citation:
  ama: Bezeljak U, Loya H, Kaczmarek BM, Saunders TE, Loose M. Stochastic activation
    and bistability in a Rab GTPase regulatory network. <i>Proceedings of the National
    Academy of Sciences of the United States of America</i>. 2020;117(12):6504-6549.
    doi:<a href="https://doi.org/10.1073/pnas.1921027117">10.1073/pnas.1921027117</a>
  apa: Bezeljak, U., Loya, H., Kaczmarek, B. M., Saunders, T. E., &#38; Loose, M.
    (2020). Stochastic activation and bistability in a Rab GTPase regulatory network.
    <i>Proceedings of the National Academy of Sciences of the United States of America</i>.
    National Academy of Sciences. <a href="https://doi.org/10.1073/pnas.1921027117">https://doi.org/10.1073/pnas.1921027117</a>
  chicago: Bezeljak, Urban, Hrushikesh Loya, Beata M Kaczmarek, Timothy E. Saunders,
    and Martin Loose. “Stochastic Activation and Bistability in a Rab GTPase Regulatory
    Network.” <i>Proceedings of the National Academy of Sciences of the United States
    of America</i>. National Academy of Sciences, 2020. <a href="https://doi.org/10.1073/pnas.1921027117">https://doi.org/10.1073/pnas.1921027117</a>.
  ieee: U. Bezeljak, H. Loya, B. M. Kaczmarek, T. E. Saunders, and M. Loose, “Stochastic
    activation and bistability in a Rab GTPase regulatory network,” <i>Proceedings
    of the National Academy of Sciences of the United States of America</i>, vol.
    117, no. 12. National Academy of Sciences, pp. 6504–6549, 2020.
  ista: 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 of the United States of America. 117(12), 6504–6549.
  mla: Bezeljak, Urban, et al. “Stochastic Activation and Bistability in a Rab GTPase
    Regulatory Network.” <i>Proceedings of the National Academy of Sciences of the
    United States of America</i>, vol. 117, no. 12, National Academy of Sciences,
    2020, pp. 6504–49, doi:<a href="https://doi.org/10.1073/pnas.1921027117">10.1073/pnas.1921027117</a>.
  short: U. Bezeljak, H. Loya, B.M. Kaczmarek, T.E. Saunders, M. Loose, Proceedings
    of the National Academy of Sciences of the United States of America 117 (2020)
    6504–6549.
date_created: 2020-03-12T05:32:26Z
date_published: 2020-03-24T00:00:00Z
date_updated: 2026-04-08T07:24:55Z
day: '24'
department:
- _id: MaLo
- _id: CaBe
doi: 10.1073/pnas.1921027117
external_id:
  isi:
  - '000521821800040'
  pmid:
  - '32161136'
intvolume: '       117'
isi: 1
issue: '12'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1101/776567
month: '03'
oa: 1
oa_version: Preprint
page: 6504-6549
pmid: 1
project:
- _id: 2599F062-B435-11E9-9278-68D0E5697425
  grant_number: RGY0083/2016
  name: Reconstitution of cell polarity and axis determination in a cell-free system
publication: Proceedings of the National Academy of Sciences of the United States
  of America
publication_identifier:
  eissn:
  - 1091-6490
  issn:
  - 0027-8424
publication_status: published
publisher: National Academy of Sciences
quality_controlled: '1'
related_material:
  link:
  - description: News on IST Homepage
    relation: press_release
    url: https://ist.ac.at/en/news/proteins-as-molecular-switches/
  record:
  - id: '8341'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: Stochastic activation and bistability in a Rab GTPase regulatory network
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 117
year: '2020'
...