Evidence for the existence of two Robo3 isoforms with divergent biochemical properties

Mol Cell Neurosci. 2005 Dec;30(4):485-93. doi: 10.1016/j.mcn.2005.07.014. Epub 2005 Oct 12.


Robo3 is a member of the roundabout (Robo) family of proteins that plays a key role in axon guidance and cell migration in the developing nervous system. Recent studies have shown that Robo3 plays a crucial role in controlling axon guidance at the midline of the CNS. Here we describe and compare two human Robo3 isoforms, Robo3A and Robo3B, which differ by the insertion of 26 amino acids at the N-terminus, and these forms appear to be evolutionary conserved. We investigated the bioactivity of these isoforms and show that they have different binding properties to Slit, and that orthologs of these forms are expressed in the mouse embryo. In addition, we show that, like other members of the Robo family, Robo3 can bind homophilically, but it is also capable of binding heterophilically to Robo1 and NCAM. We propose that these properties of Robo3 may contribute to its function at the midline of the CNS.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Central Nervous System / embryology
  • Central Nervous System / metabolism
  • Conserved Sequence
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / metabolism*
  • Neural Cell Adhesion Molecules / metabolism
  • Protein Binding
  • Protein Isoforms / chemistry
  • Protein Isoforms / metabolism
  • Receptors, Immunologic / chemistry
  • Receptors, Immunologic / metabolism*
  • Sequence Homology, Amino Acid
  • Subcellular Fractions


  • Nerve Tissue Proteins
  • Neural Cell Adhesion Molecules
  • Protein Isoforms
  • ROBO3 protein, human
  • Receptors, Immunologic
  • SLIT1 protein, human
  • roundabout protein