title: The novel secreted factor MIG-18 acts with MIG-17/ADAMTS to control cell migration in Caenorhabditis elegans.
abstract: The migration of Caenorhabditis elegans gonadal distal tip cells (DTCs) offers an excellent model to study the migration of epithelial tubes in organogenesis. mig-18 mutants cause meandering or wandering migration of DTCs during gonad formation, which is very similar to that observed in animals with mutations in mig-17, which encodes a secreted metalloprotease of the ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs) family. MIG-18 is a novel secreted protein that is conserved only among nematode species. The mig-17(null) and mig-18 double mutants exhibited phenotypes similar to those in mig-17(null) single mutants. In addition, the mutations in fbl-1/fibulin-1 and let-2/collagen IV that suppress mig-17 mutations also suppressed the mig-18 mutation, suggesting that mig-18 and mig-17 function in a common genetic pathway. The Venus-MIG-18 fusion protein was secreted from muscle cells and localized to the gonadal basement membrane, a tissue distribution reminiscent of that observed for MIG-17. Overexpression of MIG-18 in mig-17 mutants and vice versa partially rescued the relevant DTC migration defects, suggesting that MIG-18 and MIG-17 act cooperatively rather than sequentially. We propose that MIG-18 may be a cofactor of MIG-17/ADAMTS that functions in the regulation of the gonadal basement membrane to achieve proper direction of DTC migration during gonadogenesis.
authors: Department of Bioscience, Kwansei Gakuin University, Sanda 669-1337, Japan.
authors: Hon-Song
authors: HS
authors: Kim
authors: Yuko
authors: Y
authors: Kitano
authors: Masataka
authors: M
authors: Mori
authors: Tomomi
authors: T
authors: Takano
authors: Thomas Edward
authors: TE
authors: Harbaugh
authors: Kae
authors: K
authors: Mizutani
authors: Haruka
authors: H
authors: Yanagimoto
authors: Sayaka
authors: S
authors: Miwa
authors: Shinji
authors: S
authors: Ihara
authors: Yukihiko
authors: Y
authors: Kubota
authors: Yukimasa
authors: Y
authors: Shibata
authors: Kohji
authors: K
authors: Ikenishi
authors: Gian
authors: G
authors: Garriga
authors: Kiyoji
authors: K
authors: Nishiwaki
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000235:genetics; D019483:Disintegrins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006066:Gonads / Q000378:metabolism; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D021381:Protein Transport; D016415:Sequence Alignment; D015398:Signal Transduction
chemical_list: D029742:Caenorhabditis elegans Proteins; D019483:Disintegrins; C410348:MIG-17 protein, C elegans; D008666:Metalloendopeptidases
keywords: ADAMTS; basement membrane; cell migration; gonadogenesis