Evidence for endogenous ADP-ribosylation of GTP-binding proteins in neuronal cell nucleus. Possible induction by membrane depolarization.
GTP-binding protein(s) recognized by antibodies against the alpha-subunits of Gi- and Go-proteins were detected in crude nuclei isolated from rat brain stem and cortex. Immunohistochemical staining indicated that in the cortex these proteins are perinuclear, or are embedded in the nuclear membrane. Evidence is presented for an endogenous ADP-ribosylation of these proteins, which competes with their PTX-catalyzed ADP-ribosylation. The endogenous reaction has the characteristics of nonenzymatic ADP-ribosylation of cysteine residues, known to involve NAD-glycohydrolase activity. In vitro experiments showed that the alpha-subunit of Go-proteins in the cell membrane also acts as a substrate of this endogenous ADP-ribosylation. The in situ effect of membrane depolarization on the nuclear GTP-binding proteins may be attributable to their depolarization-induced endogenous ADP-ribosylation, suggesting a novel signaling mechanism in neuronal cells in the central nervous system.
Cohen-Armon
M
M
Department of Physiology and Pharmacology, Neufeld Cardiac Research Institute, Tel-Aviv University, 69978 Tel-Aviv, Israel.
Hammel
I
I
Anis
Y
Y
Homburg
S
S
Dekel
N
N
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D000818:Animals; D001496:Batrachotoxins / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D001933:Brain Stem / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D019204:GTP-Binding Proteins / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials; D051379:Mice; D009243:NAD / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D037342:Pertussis Toxin; D011188:Potassium / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D010566:Virulence Factors, Bordetella / Q000378:metabolism
D001496:Batrachotoxins; D010566:Virulence Factors, Bordetella; D009243:NAD; D000246:Adenosine Diphosphate Ribose; C031775:batrachotoxinin A 20-alpha-benzoate; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D011188:Potassium