Regulation of brain G-protein go by Alzheimer's disease gene presenilin-1.
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.
Smine
A
A
The Lerner Research Institute, Department of Neurosciences, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Xu
X
X
Nishiyama
K
K
Katada
T
T
Gambetti
P
P
Yadav
S P
SP
Wu
X
X
Shi
Y C
YC
Yasuhara
S
S
Homburger
V
V
Okamoto
T
T
D000544:Alzheimer Disease / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism*; D019556:COS Cells; D002478:Cells, Cultured; D017124:Conserved Sequence; D000939:Epitopes / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009842:Oligopeptides; D010455:Peptides / Q000378:metabolism; D053764:Presenilin-1; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014862:Wasp Venoms / Q000737:chemistry
D000939:Epitopes; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009842:Oligopeptides; C508853:PSEN1 protein, human; D010455:Peptides; D053764:Presenilin-1; D011994:Recombinant Proteins; D014862:Wasp Venoms; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C037500:mastoparan; C085706:FLAG peptide; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D019206:GTP-Binding Protein alpha Subunits, Gi-Go