Taipoxin induces F-actin fragmentation and enhances release of catecholamines in bovine chromaffin cells.
Adrenomedullary bovine chromaffin cells were used to study the uptake and cellular effects of the phospholipase type A2 (PLA2) neurotoxin taipoxin in a neuroendocrine model. This toxin entered rapidly inside cultured cells. Within 1 h, taipoxin accumulated on the plasma membrane, independently of calcium presence, and caused fragmentation of the F-actin cytoskeleton. Toxin-induced cell death occurred after 24 h of incubation with the appearance of toxin containing large vesicles. Secretory experiments performed in cell populations showed an increased exocytosis in taipoxin-treated cells stimulated by depolarization or by incubation with the calcium-ionophore A23187. Like F-actin fragmentation, this effect is abolished by replacement of Ca2+ with Sr2+ during toxin incubation. The effect of taipoxin on exocytosis is not enhanced by latrunculin A, a F-actin disassembling drug altering secretion. Secretory studies in single taipoxin-treated cells using amperometry, showed an increase in the number of released vesicles without modification of the kinetic parameters of individual vesicle fusions. Taken together, these results suggest that taipoxin causes F-actin fragmentation and enhances secretion by redistribution of vesicles among secretory pools.
Neco
Patricia
P
Instituto de Neurociencias, Centro Mixto CSIC-Universidad Miguel Hernández, Alicante, Spain.
Rossetto
Ornella
O
Gil
Anabel
A
Montecucco
Cesare
C
Gutiérrez
Luis M
LM
D000199:Actins / Q000378:metabolism*; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D016923:Cell Death; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D004072:Digitonin / Q000494:pharmacology; D004546:Elapid Venoms / Q000494:pharmacology*; D004563:Electrochemistry; D005089:Exocytosis / Q000187:drug effects; D008561:Membrane Fusion / Q000187:drug effects; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology*; D022142:Secretory Vesicles / Q000187:drug effects / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines
D000199:Actins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002395:Catecholamines; D004546:Elapid Venoms; D009466:Neuromuscular Blocking Agents; D013844:Thiazoles; D053778:Thiazolidines; C015523:taipoxin; D004072:Digitonin; C037067:latrunculin A; D002118:Calcium