The neural cell recognition molecule neurofascin interacts with syntenin-1 but not with syntenin-2, both of which reveal self-associating activity

J Biol Chem. 2001 Apr 6;276(14):10646-54. doi: 10.1074/jbc.M010647200. Epub 2001 Jan 4.

Abstract

Neurofascin belongs to the L1 subgroup of the immunoglobulin superfamily of cell adhesion molecules and is implicated in axonal growth and fasciculation. We used yeast two-hybrid screening to identify proteins that interact with neurofascin intracellularly and therefore might link it to trafficking, spatial targeting, or signaling pathways. Here, we demonstrate that rat syntenin-1, previously published as syntenin, mda-9, or TACIP18 in human, is a neurofascin-binding protein that exhibits a wide-spread tissue expression pattern with a relative maximum in brain. Syntenin-1 was found not to interact with other vertebrate members of the L1 subgroup such as L1 itself or NrCAM. We confirmed the specificity of the neurofascin-syntenin-1 interaction by ligand-overlay assay, surface plasmon resonance analysis, and colocalization of both proteins in heterologous cells. The COOH terminus of neurofascin was mapped to interact with the second PDZ domain of syntenin-1. Furthermore, we isolated syntenin-2 that may be expressed in two isoforms. Despite their high sequence similarity to syntenin-1, syntenin-2alpha, which interacts with neurexin I, and syntenin-2beta do not bind to neurofascin or several other transmembrane proteins that are binding partners of syntenin-1. Finally, we report that syntenin-1 and -2 both form homodimers and can interact with each other.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Adhesion Molecules / chemistry
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Intracellular Signaling Peptides and Proteins*
  • Membrane Proteins*
  • Molecular Sequence Data
  • Nerve Growth Factors / chemistry
  • Nerve Growth Factors / genetics
  • Nerve Growth Factors / metabolism*
  • Neurons / metabolism
  • Protein Binding
  • Rats
  • Saccharomyces cerevisiae
  • Sequence Analysis
  • Structure-Activity Relationship
  • Syntenins

Substances

  • Carrier Proteins
  • Cell Adhesion Molecules
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Nerve Growth Factors
  • Nfasc protein, rat
  • SDCBP protein, human
  • Syntenins

Associated data

  • GENBANK/AJ292243
  • GENBANK/AJ292244
  • GENBANK/AJ292245