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-subu nits of G(i)- and G(o)-proteins were detected in crude nuclei isolated from rat brain stem and cortex. Immunohistochemical staining indicate d that in the cortex these proteins are perinuclear, or are embedded i n the nuclear membrane. Evidence is presented for an endogenous ADP-ri bosylation of these proteins, which competes with their PTX-catalyzed ADP-ribosylation. The endogenous reaction has the characteristics of n onenzymatic ADP-ribosylation of cysteine residues, known to involve NA D-glycohydrolase activity. In vitro experiments showed that the alpha- subunit of G(o)-proteins in the cell membrane also acts as a substrate of this endogenous ADP-ribosylation. The in situ effect of membrane d epolarization on the nuclear GTP-binding proteins may be attributable to their depolarization-induced endogenous ADP-ribosylation, suggestin g a novel signaling mechanism in neuronal cells in the central nervous system.