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Nat Commun. 2013;4:1358. doi: 10.1038/ncomms2347.

Rab9 and retromer regulate retrograde trafficking of luminal protein required for epithelial tube length control.

Author information

1
Laboratory for Morphogenetic Signaling, Riken Center for Developmental Biology, 2-2-3 Minatojima-minamimachi, Chuo-ku, Hyogo, Kobe 650-0047, Japan.

Abstract

Apical extracellular matrix filling the lumen controls the morphology and geometry of epithelial tubes during development, yet the regulation of luminal protein composition and its role in tube morphogenesis are not well understood. Here we show that an endosomal-retrieval machinery consisting of Rab9, retromer and actin nucleator WASH (Wiskott-Aldrich Syndrome Protein and SCAR Homolog) regulates selective recycling of the luminal protein Serpentine in the Drosophila trachea. Secreted Serpentine is endocytosed and sorted into the late endosome. Vps35, WASH and actin filaments differentially localize at the Rab9-enriched subdomains of the endosomal membrane, where Serpentine containing vesicles bud off. In Rab9, Vps35 and WASH mutants, Serpentine was secreted normally into the tracheal lumen, but the luminal quantities were depleted at later stages, resulting in excessively elongated tubes. In contrast, secretion of many luminal proteins was unaffected, suggesting that retrograde trafficking of a specific class of luminal proteins is a pivotal rate-limiting mechanism for continuous tube length regulation.

PMID:
23322046
PMCID:
PMC3562448
DOI:
10.1038/ncomms2347
[Indexed for MEDLINE]
Free PMC Article

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