ArticlePloS one2010
Delayed onset of positive feedback activation of Rab5 by Rabex-5 and Rabaptin-5 in endocytosis.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 27 citations in OpenAlex.
- Lipid turnover and GEF recruitment collectively determine Rab5 recruitment and activation during the first step of early endosome formation.Nature communications · 2026Article
- ESCRTing the RABs through conversion.Biochemical Society transactions · 2025Review
- Stochastic activation and bistability in a Rab GTPase regulatory network.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Interlinked GTPase cascades provide a motif for both robust switches and oscillators.Journal of the Royal Society, Interface · 2019Article
- Differential uptake, kinetics and mechanisms of intracellular trafficking of next-generation antisense oligonucleotides across human cancer cell lines.Nucleic acids research · 2019Article
- Article
- Vinculin and Rab5 complex is required [correction of requited]for uptake of Staphylococcus aureus and interleukin-6 expression.PloS one · 2014Article
- A Rab8 guanine nucleotide exchange factor-effector interaction network regulates primary ciliogenesis.The Journal of biological chemistry · 2012Article
- The ubiquitin/proteasome system mediates entry and endosomal trafficking of Kaposi's sarcoma-associated herpesvirus in endothelial cells.PLoS pathogens · 2012Article
- Real-time imaging of Rab5 activity using a prequenched biosensor.ACS chemical biology · 2011Article
- Ubiquitination: Added complexity in Ras and Rho family GTPase function.Small GTPases · 2011Article
- The chemical master equation approach to nonequilibrium steady-state of open biochemical systems: linear single-molecule enzyme kinetics and nonlinear biochemical reaction networks.International journal of molecular sciences · 2010Review
- Signal transduction: RABGEF1 fingers RAS for ubiquitination.Current biology : CB · 2010Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundRabex-5 is a guanine nucleotide exchange factor (GEF) that specifically activates Rab5, i.e., converting Rab5-GDP to Rab5-GTP, through two distinct pathways to promote endosome fusion and endocytosis. The direct pathway involves a pool of membrane-associated Rabex-5 that targets to the membrane via an early endosomal targeting (EET) domain. The indirect pathway, on the other hand, involves a cytosolic pool of Rabex-5/Rabaptin-5 complex. The complex is recruited to the membrane via Rabaptin-5 binding to Rab5-GTP, suggesting a positive feedback mechanism. The relationship of these two pathways for Rab5 activation in the cell is unclear. METHODOLOGY/PRINCIPAL
findingsWe dissect the relative contribution of each pathway to Rab5 activation via mathematical modeling and kinetic analysis in the cell. These studies show that the indirect pathway constitutes a positive feedback loop for converting Rab5-GDP to Rab5-GTP on the endosomal membrane and allows sensitive regulation of endosome fusion activity by the levels of Rab5 and Rabex-5 in the cell. The onset of this positive feedback effect, however, contains a threshold, which requires above endogenous levels of Rab5 or Rabex-5 in the cell. We term this novel phenomenon "delayed response". The presence of the direct pathway reduces the delay by increasing the basal level of Rab5-GTP, thus facilitates the function of the Rabex-5/Rabaptin-5-mediated positive feedback loop.
conclusionOur data support the mathematical model. With the model's guidance, the data reveal the affinity of Rabex-5/Rabaptin-5/Rab5-GTP interaction in the cell, which is quantitatively related to the Rabex-5 concentration for the onset of the indirect positive feedback pathway. The presence of the direct pathway and increased Rab5 concentration can reduce the Rabex-5 concentration required for the onset of the positive feedback loop. Thus the direct and indirect pathways cooperate in the regulation of early endosome fusion.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.