D.G. and I.L. contributed equally to this work.
Glycogen synthase kinase 3 activation is essential for the snake phospholipase A2 neurotoxin-induced secretion in chromaffin cells
Article first published online: 16 APR 2007
European Journal of Neuroscience
Volume 25, Issue 8, pages 2341–2348, April 2007
How to Cite
Giner, D., López, I., Ñeco, P., Rossetto, O., Montecucco, C. and Gutiérrez, L. M. (2007), Glycogen synthase kinase 3 activation is essential for the snake phospholipase A2 neurotoxin-induced secretion in chromaffin cells. European Journal of Neuroscience, 25: 2341–2348. doi: 10.1111/j.1460-9568.2007.05497.x
- Issue published online: 16 APR 2007
- Article first published online: 16 APR 2007
- Received 8 May 2006,revised 19 February 2007,accepted 21 February 2007
- bovine chromaffin cells;
- phospholipase A2 neurotoxins;
- snake venoms
Neuroendocrine chromaffin cells were used to study the mechanism of the snake phospholipase A2 (PLA2) neurotoxin enhancement of exocytosis. Notexin, β-bungarotoxin, taipoxin or textilotoxin enhanced the fast release of catecholamines elicited by flash photolysis of cytosolic caged calcium. Such an increase correlates with the capacity of these neurotoxins to cause fragmentation of the F-actin cortical barrier with subsequent accumulation of vesicles in the proximity of the plasma membrane. These PLA2 neurotoxins do not act via protein kinase C activation, which is known to promote F-actin fragmentation. Lithium, RO31-8220 and SB216763, three inhibitors of the glycogen synthase kinase 3, prevent both the alteration of the F-actin peripheral cortex and the enhancement of fast release elicited by these neurotoxins. In addition, glycogen synthase kinase 3 has been detected by immunolocalization in a membranous compartment of the chromaffin cell endoplasmic reticulum (ER). These results suggest that the activation of this enzyme plays a major role in the enhancement of exocytosis of the readily releasable granules caused by PLA2 neurotoxins in neuroendocrine chromaffin cells.