Human SCAMP5, a Novel Secretory Carrier Membrane Protein, Facilitates Calcium-Triggered Cytokine Secretion by Interaction with SNARE Machinery
Human SCAMP5, a Novel Secretory Carrier Membrane Protein, Facilitates Calcium-Triggered Cytokine Secretion by Interaction with SNARE Machinery
复制标题
人类 SCAMP5 是一种新型分泌载体膜蛋白，通过与 SNARE 机制相互作用促进钙触发的细胞因子分泌。
DOI：
10.4049/jimmunol.0802002
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发表时间：
2009-03-01
影响因子：
4.4
通讯作者：
Cao, Xuetao
中科院分区：
文献类型：
--
作者：
Han, Chaofeng;Chen, Taoyong;Cao, Xuetao
免疫细胞产生的细胞因子在调节先天免疫和获得性免疫中起着关键作用。然而，控制细胞因子分泌的机制尚未完全阐明。分泌载体膜蛋白(SCAMPs)是分布广泛的整体膜分子，参与调控囊泡的转运。在这项研究中，我们报道了人SCAMP5(HSCAMP5)的功能特征，它是一种新的SCAMP蛋白，广泛表达于各种神经元和非神经元组织和细胞中。通过检测细胞因子(RANTES/CCL5和IL-1β)的分泌作为胞吐模型，我们发现hSCAMP5可以促进人上皮癌细胞、人单核细胞和小鼠巨噬细胞的钙调节信号肽细胞因子(CCL5，而不是IL-1β)的分泌。通过亚细胞分离、免疫荧光共聚焦显微镜和膜泡免疫分离方法，我们发现hSCAMP5主要定位于高尔基体相关的隔室，钙离子载体离子霉素可以触发hSCAMP5沿经典的胞吐途径从高尔基体快速移位到质膜。在hSCAMP5从高尔基体向质膜转运的过程中，hSCAMP5可与局部可溶性N-乙基马来酰亚胺敏感因子结合蛋白受体(SNARs)分子共分布并形成复合体。我们进一步证明，hSCAMP5可以通过hSCAMP5的胞浆C端尾直接与钙离子感受器突触素相互作用，从而提供了一种潜在的连接SCAMP和SNARE分子的分子机制。我们的发现表明，hSCAMP5与SNARE机制合作，参与了钙调节的含信号肽细胞因子的胞吐。免疫学杂志，2009,182：2986-2996。
Cytokines produced by immune cells play pivotal roles in the regulation of both innate and adaptive immunity. However, the mechanisms controlling secretion of cytokines have not been fully elucidated. Secretory carrier membrane proteins (SCAMPs) are widely distributed integral membrane molecules implicated in regulating vesicular transport. In this study, we report the functional characterization of human SCAMP5 (hSCAMP5), a novel SCAMP protein that is widely expressed by a variety of neuronal and nonneuronal tissues and cells. By measuring the cytokine secretion (RANTES/CCL5 and IL-1 beta) as an exocytotic model, we show that hSCAMP5 can promote the calcium-regulated signal peptide-containing cytokine (CCL5 but not IL-1 beta) secretion in human epithelial cancer cells, human monocytes, and mouse macrophages. By using subcellular fractionation, immunofluorescence confocal microscopy, and membrane vesicle immunoisolation methods, we find that hSCAMP5 is mainly localized in the Golgi-associated compartments, and the calcium ionophore ionomycin can trigger a rapid translocation of hSCAMP5 from Golgi apparatus to plasma membrane along the classical exocytosis pathway. During the translocation of hSCAMP5 from Golgi apparatus to plasma membrane, hSCAMP5 can codistribute and complex with local soluble N-ethylmaleimide sensitive factor attachment protein receptors (SNAREs) molecules. We further demonstrate that hSCAMP5 can directly interact with the calcium sensor synaptotagmins via the cytosolic C-terminal tail of hSCAMP5, thus providing a potential molecular mechanism linking SCAMPs with the SNARE molecules. Our findings suggest that hSCAMP5, in cooperation with the SNARE machinery, is involved in calcium-regulated exocytosis of signal peptide-containing cytokines. The Journal of Immunology, 2009, 182: 2986-2996.