Adenine nucleotides regulate ADP-ribosylation of membrane-bound actin and actin-binding to membranes.
Adenine nucleotides were shown to increase the ADP-ribosylation of actin by Clostridium perfringens iota and Clostridium botulinum C2 toxin in membranes from human platelets, hamster fat cells, rat liver- and rat brain cells. ATP and ATP gamma S were the most effective agents with ATP showing half-maximal and maximal effects at about 2 and 10 microM, respectively. The rank order of various adenine nucleotides were ATP = ATP gamma S > ADP > AMP-PNP >> AMP = cAMP. Guanine nucleotides showed the same rank order of potencies but were less effective than adenine nucleotides. Adenine nucleotides which increased ADP-ribosylation were able to release actin from membranes. [32P]ADP-ribosylated rabbit skeletal muscle actin, which is unable to polymerize, was used as tool to study membrane-binding of actin. The [32P]ADP-ribosylated actin bound to stripped rat liver membranes in a saturable, time- and temperature-dependent manner. ATP inhibited the binding of ADP-ribosylated actin with a half-maximal and maximal inhibitory concentration at about 50 and 300 microM, respectively. The data indicate that actin-binding to membranes is prevented or reversed in the presence of adenine nucleotides thereby increasing the accessibility of actin for ADP-ribosylation by toxins.
Schroeder
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Institut für Pharmakologie und Toxikologie, Universität des Saarlandes, Homburg-Saar/Germany.
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Aktories
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D036002:ADP Ribose Transferases; D000199:Actins / Q000032:analysis* / Q000378:metabolism*; D000227:Adenine Nucleotides / Q000494:pharmacology*; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000273:Adipose Tissue / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D001427:Bacterial Toxins / Q000378:metabolism / Q000494:pharmacology; D001792:Blood Platelets / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D001905:Botulinum Toxins / Q000378:metabolism / Q000494:pharmacology; D001921:Brain / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D003014:Clostridium botulinum / Q000378:metabolism; D003016:Clostridium perfringens / Q000378:metabolism; D006224:Cricetinae; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D010761:Phosphorus Radioisotopes; D051381:Rats; D013696:Temperature; D013997:Time Factors
D000199:Actins; D000227:Adenine Nucleotides; D001427:Bacterial Toxins; D008565:Membrane Proteins; D010761:Phosphorus Radioisotopes; C050737:iota toxin, Clostridium perfringens; D000246:Adenosine Diphosphate Ribose; C022571:adenosine 5'-O-(3-thiotriphosphate); D000255:Adenosine Triphosphate; D036002:ADP Ribose Transferases; D001905:Botulinum Toxins