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Artikel ; Online: Deterministic early endosomal maturations emerge from a stochastic trigger-and-convert mechanism.

York, Harrison M / Joshi, Kunaal / Wright, Charles S / Kreplin, Laura Z / Rodgers, Samuel J / Moorthi, Ullhas K / Gandhi, Hetvi / Patil, Abhishek / Mitchell, Christina A / Iyer-Biswas, Srividya / Arumugam, Senthil

Nature communications

2023  Band 14, Heft 1, Seite(n) 4652

Abstract: Endosomal maturation is critical for robust and timely cargo transport to specific cellular compartments. The most prominent model of early endosomal maturation involves a phosphoinositide-driven gain or loss of specific proteins on individual endosomes, ...

Abstract Endosomal maturation is critical for robust and timely cargo transport to specific cellular compartments. The most prominent model of early endosomal maturation involves a phosphoinositide-driven gain or loss of specific proteins on individual endosomes, emphasising an autonomous and stochastic description. However, limitations in fast, volumetric imaging long hindered direct whole cell-level measurements of absolute numbers of maturation events. Here, we use lattice light-sheet imaging and bespoke automated analysis to track individual very early (APPL1-positive) and early (EEA1-positive) endosomes over the entire population, demonstrating that direct inter-endosomal contact drives maturation between these populations. Using fluorescence lifetime, we show that this endosomal interaction is underpinned by asymmetric binding of EEA1 to very early and early endosomes through its N- and C-termini, respectively. In combination with agent-based simulation which supports a 'trigger-and-convert' model, our findings indicate that APPL1- to EEA1-positive maturation is driven not by autonomous events but by heterotypic EEA1-mediated interactions, providing a mechanism for temporal and population-level control of maturation.
Mesh-Begriff(e) Vesicular Transport Proteins/metabolism ; Transport Vesicles/metabolism ; Endosomes/metabolism
Chemische Substanzen Vesicular Transport Proteins
Sprache Englisch
Erscheinungsdatum 2023-08-02
Erscheinungsland England
Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID 2553671-0
ISSN 2041-1723 ; 2041-1723
ISSN (online) 2041-1723
ISSN 2041-1723
DOI 10.1038/s41467-023-40428-1
Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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