Rasp, a putative transmembrane acyltransferase, is required for Hedgehog signaling

Development. 2002 Feb;129(4):843-51.

Abstract

Members of the Hedgehog (Hh) family encode secreted molecules that act as potent organizers during vertebrate and invertebrate development. Post-translational modification regulates both the range and efficacy of Hh protein. One such modification is the acylation of the N-terminal cysteine of Hh. In a screen for zygotic lethal mutations associated with maternal effects, we have identified rasp, a novel Drosophila segment polarity gene. Analysis of the rasp mutant phenotype, in both the embryo and wing imaginal disc demonstrates that rasp does not disrupt Wnt/Wingless signaling but is specifically required for Hh signaling. The requirement of rasp is restricted only to those cells that produce Hh; hh transcription, protein levels and distribution are not affected by the loss of rasp. Molecular analysis reveals that rasp encodes a multipass transmembrane protein that has homology to a family of membrane bound O-acyl transferases. Our results suggest that Rasp-dependent acylation is necessary to generate a fully active Hh protein.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acyltransferases / genetics
  • Acyltransferases / metabolism*
  • Amino Acid Sequence
  • Animals
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / embryology
  • Drosophila melanogaster / metabolism
  • Hedgehog Proteins
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Molecular Sequence Data
  • Phenotype
  • Proto-Oncogene Proteins / metabolism
  • Signal Transduction*
  • Transcriptional Activation
  • Wnt1 Protein

Substances

  • Drosophila Proteins
  • Hedgehog Proteins
  • Membrane Proteins
  • Proto-Oncogene Proteins
  • Wnt1 Protein
  • rasp protein, Drosophila
  • wg protein, Drosophila
  • hh protein, Drosophila
  • Acyltransferases