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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Amidohydrolases / metabolism*
  • Animals
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / anatomy & histology*
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / embryology
  • Drosophila melanogaster / metabolism
  • Embryo, Nonmammalian / cytology
  • Embryo, Nonmammalian / metabolism
  • Endocytosis
  • Endosomes / metabolism
  • Epithelium / anatomy & histology*
  • Epithelium / embryology
  • Epithelium / metabolism
  • Green Fluorescent Proteins / metabolism
  • Multiprotein Complexes / metabolism*
  • Protein Binding
  • Protein Transport
  • Trachea / anatomy & histology*
  • Trachea / cytology
  • Trachea / embryology
  • Vesicular Transport Proteins / metabolism
  • rab GTP-Binding Proteins / metabolism*
  • trans-Golgi Network / metabolism

Substances

  • Actins
  • Drosophila Proteins
  • Multiprotein Complexes
  • Vesicular Transport Proteins
  • Vps35 protein, Drosophila
  • WASH protein, Drosophila
  • Green Fluorescent Proteins
  • Amidohydrolases
  • serp protein, Drosophila
  • Rab9 protein, Drosophila
  • rab GTP-Binding Proteins