SNX-BAR-mediated endosome tubulation is coordinated with endosome maturation

JRT van Weering, P Verkade, PJ Cullen

Research output: Contribution to journalArticle (Academic Journal)peer-review

122 Citations (Scopus)


Endosomal sorting is essential for cell homeostasis. Proteins targeted for degradation are retained in the maturing endosome vacuole while others are recycled to the cell surface or sorted to the biosynthetic pathway via tubular transport carriers. Sorting nexin (SNX) proteins containing a BAR (for Bin-Amphiphysin-Rvs) domain are key regulators of phosphoinositide-mediated, tubular-based endosomal sorting, but how such sorting is coordinated with endosomal maturation is not known. Here, using well-defined Rab GTPases as endosomal compartment markers, we have analyzed the localization of SNX1 (endosome-to-TGN transport as part of the SNX-BAR-retromer complex), SNX4 (cargo-recycling from endosomes to the plasma membrane) and SNX8 (endosomes-to-TGN trafficking in a retromer-independent manner). We show that these SNX-BARs are primarily localized to early endosomes, but display the highest frequency of tubule formation at the moment of early-to-late endosome transition: the Rab5-to-Rab7 switch. Perturbing this switch shifts SNX-BAR tubulation to early endosomes, resulting in SNX1-decorated tubules that lack retromer components VPS26 and VPS35, suggesting that both early and late endosomal characteristics of the endosome are important for SNX-BAR-retromer-tubule formation. We also establish that SNX4, but not SNX1 and SNX8, is associated with the Rab11-recycling endosomes and that a high frequency of SNX4-mediated tubule formation is observed as endosomes undergo Rab4-to-Rab11 transition. Our study therefore provides evidence for fine-tuning between the processes of endosomal maturation and the formation of endosomal tubules. Since tubulation is required for SNX1, SNX4 and SNX8-mediated sorting, these data reveal a previously unrecognized coordination between maturation and tubular-based sorting.
Translated title of the contributionSNX-BAR-mediated endosome tabulation is coordinated with endosome maturation
Original languageEnglish
Pages (from-to)94 - 107
Number of pages14
Publication statusPublished - Jan 2012

Bibliographical note

Other: First published on-line 31 October 2011


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