Institut des Neurosciences Cellulaires et Intégratives, Centre National de la Recherche Scientifique (UPR-3212), Université de Strasbourg, 5 rue Blaise Pascal, 67084 Strasbourg, France.
Biochem Soc Trans. 2010 Feb;38(Pt 1):167-71. doi: 10.1042/BST0380167.
Exocytosis of hormones occurs through the fusion of large dense-core secretory vesicles with the plasma membrane. This highly regulated process involves key proteins such as SNAREs (soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptors) and also specific lipids at the site of membrane fusion. Among the different lipids required for exocytosis, our recent observations have highlighted the crucial role of PA (phosphatidic acid) in the late stages of membrane fusion in various exocytotic events. An RNAi (RNA interference) strategy coupled with the detection of PA in living cells has pointed to plasma membrane-associated PLD1 (phospholipase D(1)) as the main producer of PA in response to secretagogue stimulation. We have identified several GTPases which regulate the activation level of PLD(1) in neuroendocrine cells. Finally, RSK2 (ribosomal S6 kinase 2) appears to phosphorylate and regulate the activity of PLD(1) in a calcium-dependent manner. Altogether our results have unravelled a complex set of regulatory pathways controlling the synthesis of fusogenic lipids at the secretory granule fusion site by PLD(1).
激素的胞吐作用是通过大致密核心分泌小泡与质膜融合来实现的。这个高度调控的过程涉及关键蛋白，如 SNAREs（可溶性 N-乙基马来酰亚胺敏感融合蛋白附着蛋白受体），以及膜融合部位的特定脂质。在胞吐作用所需的不同脂质中，我们最近的观察结果强调了 PA（磷酸脂）在各种胞吐事件中膜融合后期的关键作用。一种与活细胞中 PA 检测相结合的 RNAi（RNA 干扰）策略表明，质膜相关的 PLD1（磷脂酶 D(1)）是对刺激物作出反应时产生 PA 的主要酶。我们已经鉴定出几种 GTPases，它们调节神经内分泌细胞中 PLD(1)的激活水平。最后，RSK2（核糖体 S6 激酶 2）似乎以依赖钙的方式磷酸化并调节 PLD(1)的活性。总之，我们的研究结果揭示了一套复杂的调控途径，控制着 PLD(1)在分泌颗粒融合部位合成融合脂质。
