The function of a Drosophila glypican does not depend entirely on heparan sulfate modification

Dev Biol. 2006 Dec 15;300(2):570-82. doi: 10.1016/j.ydbio.2006.09.011. Epub 2006 Sep 15.

Abstract

Division abnormally delayed (Dally) is one of two glycosylphosphatidylinositol (GPI)-linked heparan sulfate proteoglycans in Drosophila. Numerous studies have shown that it influences Decapentaplegic (Dpp) and Wingless signaling. It has been generally assumed that Dally affects signaling by directly interacting with these growth factors, primarily through its heparan sulfate (HS) chains. To understand the functional contributions of HS chains and protein core we have (1) assessed the growth factor binding properties of purified Dally using surface plasmon resonance, (2) generated a form of Dally that is not HS modified and evaluated its signaling capacity in vivo. Purified Dally binds directly to FGF2, FGF10, and the functional Dpp homolog BMP4. FGF binding is abolished by preincubation with HS, but BMP4 association is partially HS-resistant, suggesting the Dally protein core contributes to binding. Cell binding and co-immunoprecipitation studies suggest that non-HS-modified Dally retains some ability to bind Dpp or BMP4. Expression of HS-deficient Dally in vivo showed it does not promote signaling as well as wild-type Dally, yet it can rescue several dally mutant phenotypes. These data reveal that heparan sulfate modification of Dally is not required for all in vivo activities and that significant functional capacity resides in the protein core.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Line
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / genetics
  • Drosophila Proteins / physiology*
  • Glypicans / chemistry
  • Glypicans / genetics
  • Glypicans / physiology*
  • Heparitin Sulfate / chemistry
  • Heparitin Sulfate / metabolism*
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / physiology*
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Proteoglycans / chemistry
  • Proteoglycans / genetics
  • Proteoglycans / physiology*
  • Structure-Activity Relationship

Substances

  • Drosophila Proteins
  • Glypicans
  • Membrane Glycoproteins
  • Proteoglycans
  • dally protein, Drosophila
  • Heparitin Sulfate