期刊
GENETICS
卷 203, 期 4, 页码 1789-+出版社
GENETICS SOCIETY AMERICA
DOI: 10.1534/genetics.116.192559
关键词
tubulogenesis; trafficking; endosomes; IRG; immunity-related GTPase
资金
- National Institute of General Medical Sciences [P41-GM-103311]
- NIH Office of Research Infrastructure Programs [P40-OD-010440]
- National Institutes of Health (NIH) [R03-NS-067323]
- National Science Foundation
- University of Kansas Graduate Research Fund [2301744]
- NIH Initiative for Maximizing Student Development Program [R25-GM-62232]
- NIH [OD-010943]
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.
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