A competition network connects Rab5 and Rab11 GTPases at the surface of endocytic structures

Specificity in membrane trafficking relies on the interaction between Rab small GTPase proteins and their molecular effectors. However, the evidence that different Rab proteins can bind to common effectors challenges this view. Here, we show that molecular competition between distinct Rab GTPases for a shared protein can link diverse membrane trafficking pathways. Theoretical analysis and experimental data support a role for Zfyve26 as a part of a competitive network that modulates changes in Rab5-Rab11 abundance, activation status, and correlation at the surface of single endocytic structures. By leveraging on the Loop index, a novel metric that couples the GTP-bound fraction and the total amount of Rab GTPase, we infer the saturation of Zfyve26 molecules at the endocytic surface from time-lapse imaging data. Our findings establish that transduction in the endocytic system is governed by stoichiometric constraints determining the trade-off between different trafficking pathways at the surface of a membrane-bound organelle.

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Publication Details

Journal
iScience
Published
2025-03-06
DOI
https://doi.org/10.1016/j.isci.2025.112170
Citations
1
Primary Topic
Cellular transport and secretion
Type
article
Field-Weighted Citation Impact
1.15

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article

A competition network connects Rab5 and Rab11 GTPases at the surface of endocytic structures

Andrea Pagnani, Simone Tealdi, A. Gamba, Irene Franco et al.
1 citations
iScience
Cellular transport and secretion
1.15
article

A competition network connects Rab5 and Rab11 GTPases at the surface of endocytic structures

Andrea Pagnani, Simone Tealdi, A. Gamba, Irene Franco, Carlo Cosimo Campa, Chiara Enrico Bena, Elsi Ferro, Jean Piero Margaria, Carla Bosia, Maria Chiara De Santis, Emilio Hirsch, Luca Gozzelino, Marta Cunial
article en
1 citations

Abstract

Specificity in membrane trafficking relies on the interaction between Rab small GTPase proteins and their molecular effectors. However, the evidence that different Rab proteins can bind to common effectors challenges this view. Here, we show that molecular competition between distinct Rab GTPases for a shared protein can link diverse membrane trafficking pathways. Theoretical analysis and experimental data support a role for Zfyve26 as a part of a competitive network that modulates changes in Rab5-Rab11 abundance, activation status, and correlation at the surface of single endocytic structures. By leveraging on the Loop index, a novel metric that couples the GTP-bound fraction and the total amount of Rab GTPase, we infer the saturation of Zfyve26 molecules at the endocytic surface from time-lapse imaging data. Our findings establish that transduction in the endocytic system is governed by stoichiometric constraints determining the trade-off between different trafficking pathways at the surface of a membrane-bound organelle.

iScienceVol. 28(4)
Vita-Salute San Raffaele University (IT), Istituto Nazionale di Fisica Nucleare (IT), Politecnico di Torino (IT), Istituto Nazionale di Fisica Nucleare, Sezione di Torino (IT), Italian institute for Genomic Medicine (IT), IRCCS Ospedale San Raffaele (IT), Candiolo Cancer Institute (IT), University of Turin (IT)
Fondazione Telethon, Associazione Italiana per la Ricerca sul Cancro
Openalex Percentile: Top 27%
Cellular transport and secretion
1.15
DOIOpen Access PDFOpenAlex
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