Regulation of brain G-protein go by Alzheimer's disease gene presenilin-1

J Biol Chem. 1998 Jun 26;273(26):16281-8. doi: 10.1074/jbc.273.26.16281.

Abstract

To investigate a possible association between G-proteins and presenilin-1 (PS-1), a series of glutathione S-transferase-fusion proteins containing portions of PS-1 were prepared and used in vitro in binding experiments with tissue and recombinant G-proteins. The results demonstrate that the 39 C-terminal amino acids of PS-1 selectively bind the brain G-protein, Go. Addition of guanosine 5'-3-O-(thio)triphosphate promoted Go dissociation from PS-1, indicating that this domain mimics the function of G-protein-coupling domains found in receptors. The 39-amino acid synthetic polypeptide activated Go in a magnesium ion-dependent manner. Physical interaction of full-length PS-1 and Go was also demonstrated. Following transfection of Goalpha and N-terminally FLAG-tagged PS-1 in COS-7 cells, Go was immunoprecipitated by FLAG antibodies. In addition, endogenous PS-1 and Goalpha were colocalized immunocytochemically in human glioma cell lines. The results indicate that PS-1 regulates Go activities in living cells.

Publication types

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

MeSH terms

  • Alzheimer Disease / genetics*
  • Amino Acid Sequence
  • Animals
  • Brain / metabolism*
  • COS Cells
  • Cells, Cultured
  • Conserved Sequence
  • Epitopes / metabolism
  • GTP Phosphohydrolases / metabolism
  • GTP-Binding Protein alpha Subunits, Gi-Go / metabolism
  • GTP-Binding Proteins / genetics*
  • GTP-Binding Proteins / metabolism
  • Gene Expression Regulation*
  • Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Molecular Sequence Data
  • Oligopeptides
  • Peptides / metabolism
  • Presenilin-1
  • Rats
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Wasp Venoms / chemistry

Substances

  • Epitopes
  • Intercellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Oligopeptides
  • PSEN1 protein, human
  • Peptides
  • Presenilin-1
  • Recombinant Proteins
  • Wasp Venoms
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • mastoparan
  • FLAG peptide
  • GTP Phosphohydrolases
  • GTP-Binding Proteins
  • GTP-Binding Protein alpha Subunits, Gi-Go