Marine toxins and the cytoskeleton: okadaic acid and dinophysistoxins.
Okadaic acid (OA) and its analogs, the dinophysistoxins, are potent inhibitors of protein phosphatases 1 and 2A. This action is well known to cause diarrhea and gastrointestinal symptons when the toxins reach the digestive tract by ingestion of mollusks. A less well-known effect of these group of toxins is their effect in the cytoskeleton. OA has been shown to stimulate cell motility, loss of stabilization of focal adhesions and a consequent loss of cytoskeletal organization due to an alteration in the tyrosine-phosphorylated state of the focal adhesion kinases and paxillin. OA causes cell rounding and loss of barrier properties through mechanisms that probably involve disruption of filamentous actin (F-actin) and/or hyperphosphorylation and activation of kinases that stimulate tight junction disassembly. Neither methyl okadaate (a weak phosphatase inhibitor) nor OA modify the total amount of F-actin, but both toxins cause similar changes in the F-actin cytoskeleton, with strong retraction and rounding, and in many cases cell detachment. OA and dinophysistoxin-1 (35S-methylokadaic acid) cause rapid changes in the structural organization of intermediate filaments, followed by a loss of microtubules, solubilization of intermediate filament proteins, and disruption of desmosomes. The detailed pathways that coordinate all these effects are not yet known.
Vale
Carmen
C
Departamento de Farmacología, Facultad de Veterinaria, USC, Lugo, Spain. mdelcarmen.vale@usc.es
Botana
Luis M
LM
D000199:Actins / Q000187:drug effects; D000818:Animals; D045744:Cell Line, Tumor; D003599:Cytoskeleton / Q000187:drug effects / Q000473:pathology; D003967:Diarrhea / Q000139:chemically induced; D006801:Humans; D008387:Marine Toxins / Q000633:toxicity*; D008974:Mollusca; D019319:Okadaic Acid / Q000633:toxicity*; D054645:Protein Phosphatase 1 / Q000037:antagonists & inhibitors; D054648:Protein Phosphatase 2 / Q000037:antagonists & inhibitors; D012758:Shellfish
D000199:Actins; D008387:Marine Toxins; D019319:Okadaic Acid; D054645:Protein Phosphatase 1; D054648:Protein Phosphatase 2