AI Article Synopsis
- Fusogenic cone-shaped lipids like phosphatidic acid (PA) and SNARE proteins are essential for membrane fusion during exocytosis.
- Phospholipase D (PLD), primarily activated by ribosomal S6 kinase 2 (RSK2), is responsible for synthesizing PA in neuroendocrine cells.
- Depletion of RSK2 significantly hinders PA production and inhibits hormone release, but using phosphomimetic mutants of PLD1 can restore secretion, emphasizing RSK2's role in activating PLD1 for exocytosis.
Article Abstract
Together with the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins, fusogenic cone-shaped lipids, such as phosphatidic acid (PA), have been recently shown to be important actors in membrane fusion during exocytosis. Phospholipase D (PLD) appears to be the main provider of PA at the exocytotic site in neuroendocrine cells. We show here that ribosomal S6 kinase 2 (RSK2) stimulates PLD activity through the phosphorylation of Thr147 in the PLD1 amino-terminal Phox-homology domain. In PC12 cells, depletion of RSK2 dramatically prevents PA synthesis at exocytotic sites and inhibits hormone release. Expression of PLD1 phosphomimetic mutants fully restores secretion in cells depleted of RSK2, suggesting that RSK2 is a critical upstream signaling element in the activation of PLD1 to produce the lipids required for exocytosis.
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| http://dx.doi.org/10.1111/j.1749-6632.2008.04001.x | DOI Listing |
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