Alternative splicing of Drosophila Dscam generates axon guidance receptors that exhibit isoform-specific homophilic binding

Cell. 2004 Sep 3;118(5):619-33. doi: 10.1016/j.cell.2004.08.021.


Dscam is an immunoglobulin (Ig) superfamily protein required for the formation of neuronal connections in Drosophila. Through alternative splicing, Dscam potentially gives rise to 19,008 different extracellular domains linked to one of two alternative transmembrane segments, resulting in 38,016 isoforms. All isoforms share the same domain structure but contain variable amino acid sequences within three Ig domains in the extracellular region. We demonstrate that different isoforms exhibit different binding specificity. Each isoform binds to itself but does not bind or binds poorly to other isoforms. The amino acid sequences of all three variable Ig domains determine binding specificity. Even closely related isoforms sharing nearly identical amino acid sequences exhibit isoform-specific binding. We propose that this preferential homophilic binding specificity regulates interactions between cells and contributes to the formation of complex patterns of neuronal connections.

Publication types

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

MeSH terms

  • Alternative Splicing / genetics*
  • Amino Acid Sequence / genetics
  • Animals
  • Binding Sites / genetics
  • COS Cells
  • Cell Adhesion Molecules
  • Cell Communication / genetics
  • Cell Differentiation / genetics
  • Cell Membrane / genetics
  • Cell Membrane / metabolism
  • Drosophila Proteins*
  • Drosophila melanogaster
  • Embryo, Nonmammalian / cytology
  • Embryo, Nonmammalian / embryology*
  • Embryo, Nonmammalian / metabolism
  • Gene Expression Regulation, Developmental / genetics
  • Growth Cones / metabolism*
  • Growth Cones / ultrastructure
  • Nervous System / cytology
  • Nervous System / embryology*
  • Nervous System / metabolism
  • Protein Binding / genetics
  • Protein Biosynthesis
  • Protein Isoforms / biosynthesis
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Structure, Tertiary / genetics
  • Proteins / genetics*
  • Receptors, Cell Surface / biosynthesis
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*


  • Cell Adhesion Molecules
  • Drosophila Proteins
  • Dscam1 protein, Drosophila
  • Protein Isoforms
  • Proteins
  • Receptors, Cell Surface