title: C. elegans mig-6 encodes papilin isoforms that affect distinct aspects of DTC migration, and interacts genetically with mig-17 and collagen IV.
abstract: The gonad arms of C. elegans hermaphrodites acquire invariant shapes by guided migrations of distal tip cells (DTCs), which occur in three phases that differ in the direction and basement membrane substrata used for movement. We found that mig-6 encodes long (MIG-6L) and short (MIG-6S) isoforms of the extracellular matrix protein papilin, each required for distinct aspects of DTC migration. Both MIG-6 isoforms have a predicted N-terminal papilin cassette, lagrin repeats and C-terminal Kunitz-type serine proteinase inhibitory domains. We show that mutations affecting MIG-6L specifically and cell-autonomously decrease the rate of post-embryonic DTC migration, mimicking a post-embryonic collagen IV deficit. We also show that MIG-6S has two separable functions - one in embryogenesis and one in the second phase of DTC migration. Genetic data suggest that MIG-6S functions in the same pathway as the MIG-17/ADAMTS metalloproteinase for guiding phase 2 DTC migrations, and MIG-17 is abnormally localized in mig-6 class-s mutants. Genetic data also suggest that MIG-6S and non-fibrillar network collagen IV play antagonistic roles to ensure normal phase 2 DTC guidance.
authors.affiliation: Samuel Lunenfeld Research Institute of Mount Sinai Hospital, Toronto, M5G 1X5, Canada.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Kawano
authors.forename: Hong
authors.initials: H
authors.lastname: Zheng
authors.forename: David C
authors.initials: DC
authors.lastname: Merz
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kohara
authors.forename: Katsuyuki K
authors.initials: KK
authors.lastname: Tamai
authors.forename: Kiyoji
authors.initials: K
authors.lastname: Nishiwaki
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Culotti
mesh_terms: D000483:Alleles; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D003001:Cloning, Molecular; D024141:Collagen Type IV / Q000235:genetics / Q000378:metabolism*; D019483:Disintegrins / Q000235:genetics / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006066:Gonads / Q000378:metabolism; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference
chemical_list: D029742:Caenorhabditis elegans Proteins; D024141:Collagen Type IV; D019483:Disintegrins; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; C410348:MIG-17 protein, C elegans; D020033:Protein Isoforms; D008666:Metalloendopeptidases