Facilitation of Endosomal Recycling by an IRG Protein Homolog Maintains Apical Tubule Structure in Caenorhabditis elegans

Genetics. 2016 Aug;203(4):1789-806. doi: 10.1534/genetics.116.192559. Epub 2016 Jun 22.

Abstract

Determination of luminal diameter is critical to the function of small single-celled tubes. A series of EXC proteins, including EXC-1, prevent swelling of the tubular excretory canals in Caenorhabditis elegans In this study, cloning of exc-1 reveals it to encode a homolog of mammalian IRG proteins, which play roles in immune response and autophagy and are associated with Crohn's disease. Mutants in exc-1 accumulate early endosomes, lack recycling endosomes, and exhibit abnormal apical cytoskeletal structure in regions of enlarged tubules. EXC-1 interacts genetically with two other EXC proteins that also affect endosomal trafficking. In yeast two-hybrid assays, wild-type and putative constitutively active EXC-1 binds to the LIM-domain protein EXC-9, whose homolog, cysteine-rich intestinal protein, is enriched in mammalian intestine. These results suggest a model for IRG function in forming and maintaining apical tubule structure via regulation of endosomal recycling.

Keywords: IRG; endosomes; immunity-related GTPase; trafficking; tubulogenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Autophagy / genetics
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans Proteins / genetics*
  • Caenorhabditis elegans Proteins / metabolism
  • Crohn Disease / genetics
  • Crohn Disease / pathology
  • Cytoskeleton / genetics
  • Cytoskeleton / metabolism
  • Endosomes / genetics*
  • Endosomes / metabolism
  • Humans
  • Kidney Tubules / growth & development
  • Kidney Tubules / metabolism
  • Metalloproteins / genetics*
  • Metalloproteins / metabolism
  • Protein Transport / genetics
  • Two-Hybrid System Techniques

Substances

  • Caenorhabditis elegans Proteins
  • Exc-9 protein, C elegans
  • Metalloproteins