Rho 鸟嘌呤核苷酸交换因子 intersectin 1L 和 β-Pix 控制神经内分泌 PC12 细胞中钙调节的胞吐作用。
The Rho guanine nucleotide exchange factors Intersectin 1L and β-Pix control calcium-regulated exocytosis in neuroendocrine PC12 cells.
机构信息
CNRS UPR 3212, Institut des Neurosciences Cellulaires et Intégratives, Université de Strasbourg, 5 rue Blaise Pascal, 67084 Strasbourg, France.
出版信息
Cell Mol Neurobiol. 2010 Nov;30(8):1327-33. doi: 10.1007/s10571-010-9580-2. Epub 2010 Nov 19.
Abstract
GTPases of the Rho family are molecular switches that play an important role in a wide range of membrane-trafficking processes including neurotransmission and hormone release. We have previously demonstrated that RhoA and Cdc42 regulate calcium-dependent exocytosis in chromaffin cells by controlling actin dynamics, whereas Rac1 regulates lipid organisation. These findings raised the question of the upstream mechanism activating these GTPases during exocytosis. The guanine nucleotide exchange factors (GEFs) that catalyse the exchange of GDP for GTP are crucial elements regulating Rho signalling. Using an RNA interference approach, we have recently demonstrated that the GEFs Intersectin-1L and β-Pix, play essential roles in neuroendocrine exocytosis by controlling the activity of Cdc42 and Rac1, respectively. This review summarizes these results and discusses the functional importance of Rho GEFs in the exocytotic machinery in neuroendocrine cells.
摘要
Rho 家族的 GTPases 是分子开关，在包括神经递质传递和激素释放在内的广泛膜运输过程中发挥重要作用。我们之前已经证明 RhoA 和 Cdc42 通过控制肌动蛋白动力学来调节嗜铬细胞中钙依赖性胞吐作用，而 Rac1 调节脂质组织。这些发现提出了一个问题，即在胞吐作用期间，激活这些 GTPases 的上游机制是什么。催化 GDP 与 GTP 交换的鸟嘌呤核苷酸交换因子 (GEF) 是调节 Rho 信号的关键元件。我们最近使用 RNA 干扰方法证明，GEF 蛋白 intersectin-1L 和 β-Pix 通过分别控制 Cdc42 和 Rac1 的活性，在神经内分泌胞吐作用中发挥重要作用。这篇综述总结了这些结果，并讨论了 Rho GEF 在神经内分泌细胞胞吐机制中的功能重要性。
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