An extracellular interactome of immunoglobulin and LRR proteins reveals receptor-ligand networks

Cell. 2013 Jul 3;154(1):228-39. doi: 10.1016/j.cell.2013.06.006.

Abstract

Extracellular domains of cell surface receptors and ligands mediate cell-cell communication, adhesion, and initiation of signaling events, but most existing protein-protein "interactome" data sets lack information for extracellular interactions. We probed interactions between receptor extracellular domains, focusing on a set of 202 proteins composed of the Drosophila melanogaster immunoglobulin superfamily (IgSF), fibronectin type III (FnIII), and leucine-rich repeat (LRR) families, which are known to be important in neuronal and developmental functions. Out of 20,503 candidate protein pairs tested, we observed 106 interactions, 83 of which were previously unknown. We "deorphanized" the 20 member subfamily of defective-in-proboscis-response IgSF proteins, showing that they selectively interact with an 11 member subfamily of previously uncharacterized IgSF proteins. Both subfamilies interact with a single common "orphan" LRR protein. We also observed interactions between Hedgehog and EGFR pathway components. Several of these interactions could be visualized in live-dissected embryos, demonstrating that this approach can identify physiologically relevant receptor-ligand pairs.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / cytology*
  • Drosophila melanogaster / embryology
  • Drosophila melanogaster / metabolism*
  • Fibronectins / chemistry
  • Fibronectins / metabolism*
  • Immunoglobulins / metabolism*
  • Ligands
  • Molecular Sequence Data
  • Phylogeny
  • Protein Interaction Maps*
  • Protein Structure, Tertiary
  • Proteins / metabolism*
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / metabolism
  • Sequence Alignment

Substances

  • Drosophila Proteins
  • Fibronectins
  • Immunoglobulins
  • Ligands
  • Proteins
  • Receptors, Cell Surface
  • leucine-rich repeat proteins