title: Facilitation of Endosomal Recycling by an IRG Protein Homolog Maintains Apical Tubule Structure in Caenorhabditis elegans.
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.
authors.affiliation: Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas 66045 Department of Biological Sciences, Minnesota State University, Mankato, Minnesota 56001.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Grussendorf
authors.affiliation: Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas 66045.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Trezza
authors.affiliation: Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas 66045.
authors.forename: Alexander T
authors.initials: AT
authors.lastname: Salem
authors.affiliation: Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas 66045.
authors.forename: Hikmat
authors.initials: H
authors.lastname: Al-Hashimi
authors.affiliation: Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas 66045.
authors.forename: Brendan C
authors.initials: BC
authors.lastname: Mattingly
authors.affiliation: Department of Biological Sciences, Minnesota State University, Mankato, Minnesota 56001.
authors.forename: Drew E
authors.initials: DE
authors.lastname: Kampmeyer
authors.affiliation: Mucosal Immunology and Biology Research Center, Developmental Biology and Genetics Core, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114.
authors.forename: Liakot A
authors.initials: LA
authors.lastname: Khan
authors.affiliation: Department of Neuroscience, Center for Caenorhabditis elegans Anatomy, Albert Einstein College of Medicine, Bronx, New York 10461.
authors.forename: David H
authors.identifier: 0000-0001-8459-9820
authors.initials: DH
authors.lastname: Hall
authors.affiliation: Mucosal Immunology and Biology Research Center, Developmental Biology and Genetics Core, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114.
authors.forename: Verena
authors.initials: V
authors.lastname: Göbel
authors.affiliation: Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas 66045.
authors.forename: Brian D
authors.identifier: 0000-0002-1257-2407
authors.initials: BD
authors.lastname: Ackley
authors.affiliation: Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas 66045 buechner@ku.edu.
authors.forename: Matthew
authors.identifier: 0000-0002-2103-9399
authors.initials: M
authors.lastname: Buechner
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D003424:Crohn Disease / Q000235:genetics / Q000473:pathology; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism; D011992:Endosomes / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007684:Kidney Tubules / Q000254:growth & development / Q000378:metabolism; D008667:Metalloproteins / Q000235:genetics* / Q000378:metabolism; D021381:Protein Transport / Q000235:genetics; D020798:Two-Hybrid System Techniques
chemical_list: D029742:Caenorhabditis elegans Proteins; C528930:Exc-9 protein, C elegans; D008667:Metalloproteins
keywords: IRG; endosomes; immunity-related GTPase; trafficking; tubulogenesis