title: Drosophila dumpy is a gigantic extracellular protein required to maintain tension at epidermal-cuticle attachment sites.
abstract: BACKGROUND
  Growth and morphogenesis during development depend both on patterning genes, which assign positional information, and on genes that regulate mechanical forces. The dumpy gene of the fruit fly Drosophila melanogaster is an example of the latter class, with mutant phenotypes affecting size and shape of the limbs, thoracic cuticle, trachea and mouthparts.
  
  
  RESULTS
  The genetically complex dumpy locus was found to span over 100 kb and encode a gigantic 2.5 MDa extracellular matrix protein. Dumpy represents an extreme form of modular protein evolution, containing 308 epidermal growth factor (EGF) modules, interspersed with a new module class, DPY, and terminating in a crosslinking zona pellucida domain and membrane anchor sequence. We determined the three-dimensional structure of the DPY module by nuclear magnetic resonance (NMR) spectroscopy and found that it forms a disulphide-stabilised beta sheet motif, capable of linking end-to-end with EGF modules to form a fibre. Consistent with its cuticle phenotypes, dumpy is expressed at several sites of cuticle-epidermal cell attachment, including the trachea and the muscle tendon cells, which mediate anchorage of the muscles to the cuticle.
  
  
  CONCLUSIONS
  The dumpy gene encodes a gigantic extracellular molecule that we predict to be a membrane-anchored fibre of almost a micrometer in length. Insertion and crosslinking of this fibre within the cuticle may provide a strong anchor for the underlying tissue, allowing it to maintain mechanical tension at sites under stress. This would explain its contribution to tissue morphogenesis through its regulation of mechanical properties.
authors.affiliation: Stopford Building, University of Manchester, School of Biological Sciences, Manchester, M13 9PT, UK.
authors.forename: M B
authors.initials: MB
authors.lastname: Wilkin
authors.forename: M N
authors.initials: MN
authors.lastname: Becker
authors.forename: D
authors.initials: D
authors.lastname: Mulvey
authors.forename: I
authors.initials: I
authors.lastname: Phan
authors.forename: A
authors.initials: A
authors.lastname: Chao
authors.forename: K
authors.initials: K
authors.lastname: Cooper
authors.forename: H J
authors.initials: HJ
authors.lastname: Chung
authors.forename: I D
authors.initials: ID
authors.lastname: Campbell
authors.forename: M
authors.initials: M
authors.lastname: Baron
authors.forename: R
authors.initials: R
authors.lastname: MacIntyre
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019457:Chromosome Breakage; D002874:Chromosome Mapping; D016386:Chromosome Walking; D003001:Cloning, Molecular; D004330:Drosophila / Q000235:genetics / Q000254:growth & development*; D029721:Drosophila Proteins; D004817:Epidermis / Q000502:physiology; D005109:Extracellular Matrix / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D017403:In Situ Hybridization; D019476:Insect Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data
chemical_list: C411950:DPY protein, Drosophila; D029721:Drosophila Proteins; D016326:Extracellular Matrix Proteins; D019476:Insect Proteins