ADP-ribosylating and glucosylating toxins as tools to study secretion in RBL cells.
The influence of different ADP-ribosylating and glucosylating cytotoxins on stimulated protein tyrosine phosphorylation and secretion in rat basophilic leukemia (RBL) cells was studied. Treatment of RBL cells with Clostridium botulinum C2 toxin, which specifically ADP-ribosylated monomeric G-actin and caused complete depolymerization of the actin cytoskeleton in intact cells, inhibited Fc epsilon RI receptor-mediated tyrosine phosphorylation of various proteins in a time- and concentration-dependent manner with maximal effects at 100 ng/ml C2I and 200 ng/ml C2I. C2 toxin (10 ng/ml C2I and 20 ng/ml C2II) increased antigen- or calcium ionophore (A23187)-stimulated [3H]serotonin release maximally by about 3 fold. Clostridium botulinum C3, which ADP-ribosylated Rho in intact RBL cells, had no effect on protein tyrosine phosphorylation and stimulated secretion. In contrast, the cytotoxic Clostridium difficile toxin B (ToxB), which glucosylated the Rho-subtype family members RhoA and Cdc42, blocked or reduced antigen- or calcium ionophore-mediated [3H]serotonin release, respectively, and decreased tyrosine phosphorylation of a 110 kDa protein. The data indicate that different actin pools control tyrosine phosphorylation and secretion in RBL cells and suggest that Rho subfamily proteins regulate secretion independently of the actin cytoskeleton.
Prepens
U
U
Institut für Pharmakologie und Toxikologie, Albert-Ludwigs-Universiät, Freiburg, Germany.
Just
I
I
Hofmann
F
F
Aktories
K
K
D036002:ADP Ribose Transferases / Q000494:pharmacology; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins; D001427:Bacterial Toxins / Q000494:pharmacology; D001491:Basophils / Q000187:drug effects / Q000378:metabolism*; D001905:Botulinum Toxins / Q000494:pharmacology*; D016360:Clostridioides difficile; D006031:Glycosylation; D015471:Leukemia, Basophilic, Acute; D010766:Phosphorylation; D011065:Poly(ADP-ribose) Polymerases / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000378:metabolism; D014407:Tumor Cells, Cultured
D001426:Bacterial Proteins; D001427:Bacterial Toxins; C031815:toxB protein, Clostridium difficile; D000246:Adenosine Diphosphate Ribose; D012701:Serotonin; D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; D011065:Poly(ADP-ribose) Polymerases; D001905:Botulinum Toxins; C096324:botulinum toxin type C