Structural Basis for Interactions Between Contactin Family Members and Protein-tyrosine Phosphatase Receptor Type G in Neural Tissues

J Biol Chem. 2016 Oct 7;291(41):21335-21349. doi: 10.1074/jbc.M116.742163. Epub 2016 Aug 18.

Abstract

Protein-tyrosine phosphatase receptor type G (RPTPγ/PTPRG) interacts in vitro with contactin-3-6 (CNTN3-6), a group of glycophosphatidylinositol-anchored cell adhesion molecules involved in the wiring of the nervous system. In addition to PTPRG, CNTNs associate with multiple transmembrane proteins and signal inside the cell via cis-binding partners to alleviate the absence of an intracellular region. Here, we use comprehensive biochemical and structural analyses to demonstrate that PTPRG·CNTN3-6 complexes share similar binding affinities and a conserved arrangement. Furthermore, as a first step to identifying PTPRG·CNTN complexes in vivo, we found that PTPRG and CNTN3 associate in the outer segments of mouse rod photoreceptor cells. In particular, PTPRG and CNTN3 form cis-complexes at the surface of photoreceptors yet interact in trans when expressed on the surfaces of apposing cells. Further structural analyses suggest that all CNTN ectodomains adopt a bent conformation and might lie parallel to the cell surface to accommodate these cis and trans binding modes. Taken together, these studies identify a PTPRG·CNTN complex in vivo and provide novel insights into PTPRG- and CNTN-mediated signaling.

Keywords: cell adhesion; cell surface; contactin; crystal structure; immunoglobulin|L-like domain; protein phosphatase; retina.

MeSH terms

  • Animals
  • Contactins* / chemistry
  • Contactins* / genetics
  • Contactins* / metabolism
  • Humans
  • Mice
  • Models, Biological
  • Models, Molecular
  • Multiprotein Complexes* / chemistry
  • Multiprotein Complexes* / genetics
  • Multiprotein Complexes* / metabolism
  • Nerve Tissue / metabolism*
  • Nerve Tissue Proteins* / chemistry
  • Nerve Tissue Proteins* / genetics
  • Nerve Tissue Proteins* / metabolism
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5* / chemistry
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5* / genetics
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5* / metabolism
  • Signal Transduction / physiology*

Substances

  • Contactins
  • Multiprotein Complexes
  • Nerve Tissue Proteins
  • Ptprg protein, mouse
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5

Associated data

  • PDB/5E5R
  • PDB/5E5U
  • PDB/5E4I
  • PDB/5E53
  • PDB/5E7L
  • PDB/5E4Q
  • PDB/5I99
  • PDB/5E4S
  • PDB/5E52
  • PDB/5E55