Facilitation of endosomal recycling by an IRG protein homolog maintains apical tubule structure in Caenorhabditis elegans

Kelly A. Grussendorf, Christopher J. Trezza, Alexander T. Salem, Hikmat Al-Hashimi, Brendan C. Mattingly, Drew E. Kampmeyer, Liakot A. Khan, David H. Hall, Verena Göbel, Brian D. Ackley, Matthew Buechner

Research output: Contribution to journalArticle

4 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1789-1806
Number of pages18
JournalGenetics
Volume203
Issue number4
DOIs
StatePublished - Aug 2016

Keywords

  • Endosomes
  • IRG
  • Immunity-related GTPase
  • Trafficking
  • Tubulogenesis

ASJC Scopus subject areas

  • Genetics

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    Grussendorf, K. A., Trezza, C. J., Salem, A. T., Al-Hashimi, H., Mattingly, B. C., Kampmeyer, D. E., Khan, L. A., Hall, D. H., Göbel, V., Ackley, B. D., & Buechner, M. (2016). Facilitation of endosomal recycling by an IRG protein homolog maintains apical tubule structure in Caenorhabditis elegans. Genetics, 203(4), 1789-1806. https://doi.org/10.1534/genetics.116.192559