Post-translational proteolytic processing of the calcium-independent receptor of alpha-latrotoxin (CIRL), a natural chimera of the cell adhesion protein and the G protein-coupled receptor. Role of the G protein-coupled receptor proteolysis site (GPS) motif

J Biol Chem. 2002 Nov 29;277(48):46518-26. doi: 10.1074/jbc.M206415200. Epub 2002 Sep 20.

Abstract

The calcium-independent receptor of alpha-latrotoxin (CIRL), a neuronal cell surface receptor implicated in the regulation of exocytosis, is a natural chimera of the cell adhesion protein and the G protein-coupled receptor (GPCR). In contrast with canonic GPCRs, CIRL consists of two heterologous non-covalently bound subunits, p120 and p85, due to endogenous proteolytic processing of the receptor precursor in the endoplasmic reticulum. Extracellularly oriented p120 contains hydrophilic cell adhesion domains, whereas p85 resembles a generic GPCR. We determined that the site of the CIRL cleavage is located within a juxtamembrane Cys- and Trp-rich domain of the N-terminal extracellular region of CIRL. Mutations in this domain make CIRL resistant to the cleavage and impair its trafficking. Therefore, we have named it GPS for G protein-coupled receptor proteolysis site. The GPS motif is found in homologous adhesion GPCRs and thus defines a novel receptor family. We postulate that the proteolytic processing and two-subunit structure is a common characteristic feature in the family of GPS-containing adhesion GPCRs.

Publication types

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

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • COS Cells
  • Cell Adhesion*
  • DNA Primers
  • GTP-Binding Proteins / metabolism*
  • Humans
  • Hydrolysis
  • Membrane Proteins
  • Molecular Sequence Data
  • Protein Processing, Post-Translational*
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / metabolism*
  • Receptors, G-Protein-Coupled
  • Receptors, Peptide / chemistry
  • Receptors, Peptide / metabolism*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism*
  • Sequence Homology, Amino Acid
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Substances

  • ADGRL1 protein, human
  • DNA Primers
  • Membrane Proteins
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • Receptors, Peptide
  • Recombinant Fusion Proteins
  • GTP-Binding Proteins