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Spatial Cycling of Rab GTPase, Driven by the GTPase Cycle, Controls Rab's Subcellular Distribution
Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Science and Technology, Department of Chemistry. Chemical Genomics Centre of the Max Planck Society, Otto-Hahn-Strasse 15, 44227 Dortmund, Germany; Max-Planck-Institute of Molecular Physiology, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany.
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2019 (English)In: Biochemistry, ISSN 0006-2960, E-ISSN 1520-4995, Vol. 58, no 4, p. 276-285Article in journal (Refereed) Published
Abstract [en]

Rab GTPases (>60 members in humans) function as master regulators of intracellular membrane trafficking. Correct and specific localization of Rab proteins is required for their function. How the distinct spatial distribution of Rab GTPases in the cell is regulated remains elusive. To globally assess the subcellular localization of Rab1, we determined kinetic parameters of two pathways that control the spatial cycles of Rabl, i.e., vesicular transport and GDP dissociation inhibitor (GDI)-mediated recycling. We demonstrate that the switching between GTP and GDP binding states, which is governed by guanine nucleotide exchange factors (GEFs), GTPase-activating proteins (GAPs), GDI, and GDI displacement factor (GDF), is a major determinant of Rab1's ability to effectively cycle between cellular compartments and eventually its subcellular distribution. In silico perturbations of vesicular transport, GEFs, GAPs, GDI, and GDF using a mathematical model with simplified cellular geometries showed that these regulators play an important role in the subcellular distribution and activity of Rab1.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2019. Vol. 58, no 4, p. 276-285
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:umu:diva-156598DOI: 10.1021/acs.biochem.8b00932ISI: 000457503600008PubMedID: 30605611OAI: oai:DiVA.org:umu-156598DiVA, id: diva2:1290450
Funder
Knut and Alice Wallenberg FoundationAvailable from: 2019-02-20 Created: 2019-02-20 Last updated: 2019-03-28Bibliographically approved

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Available from 2020-01-29 00:00

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Wu, Yao-Wen

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