清华大学医学院免疫学系，第二军医大免疫研究所，医学免疫国家重点实验室的研究者在最新一期的The Journal of Immunology上发表免疫新发现，文章标题：Human SCAMP5, a Novel Secretory Carrier Membrane Protein, Facilitates Calcium-Triggered Cytokine Secretion by Interaction with SNARE Machinery。
免疫细胞分泌细胞因子是机体天然免疫和获得性免疫的重要调节方式。然而，免疫细胞如何分泌细胞因子调节免疫系统的机制一直不被人所知。分泌载体膜蛋白（Secretory carrier membrane proteins，SCAMPs）广泛存在与细胞囊泡运输系统皱褶中的蛋白。在本篇研究性文章中，曹雪涛院士等人主要解析了人类分泌载体膜蛋白SCAMP5（hSCAMP5）的功能特征，SCAMP5是分泌载体膜蛋白的一种，广泛存在于神经组织和非神经组织细胞内。
研究发现在人类上皮癌细胞、单核细胞和小鼠巨噬细胞中SCAMP5能促进钙调节的信号肽细胞因子分泌（包括CCL5，不包括IL-1β）。研究人员用亚细胞结构分离技术，免疫荧光共聚焦显微镜检测技术，囊泡免疫分离技术，对人SCAMP5研究发现其主要定位在高尔基体的间隔室内，钙离子载体能促使hSCAMP5易位，通过经典的细胞胞吐通道使其迅速从高尔基体转移到细胞膜外。
深入的研究发现hSCAMP5能与附着蛋白受体（attachment protein receptors，SNAREs）相互作用，协助SNAREs参与改调节的胞吐作用，调节信号肽和细胞因子的分泌。（生物谷Bioon.com）
生物谷推荐原始出处：
The Journal of Immunology, 2009, 182: 2986-2996.doi:10.4049/jimmunol.0802002
Human SCAMP5, a Novel Secretory Carrier Membrane Protein, Facilitates Calcium-Triggered Cytokine Secretion by Interaction with SNARE Machinery1
Chaofeng Han2,*, Taoyong Chen2,, Mingjin Yang, Nan Li, Haibo Liu and Xuetao Cao3,*,
* Institute of Immunology, Tsinghua University School of Medicine, Beijing, People’s Republic of China; and Institute of Immunology and National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai, People’s Republic of China
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-1β) as an exocytotic model, we show that hSCAMP5 can promote the calcium-regulated signal peptide-containing cytokine (CCL5 but not IL-1β) 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.
1 This work was supported by grants from the Foundation for the Author of Excellent Doctoral Dissertation of China (200775), National Natural Science Foundation of China (30572122, 30771118, 30721091), National Key Basic Research Program of China (2007CB512403), and National Specific Program of New Drug Development and Shanghai Committee of Science and Technology (07QA14067).
2 These authors contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Xuetao Cao, Institute of Immunology, Tsinghua University School of Medicine, Beijing, People’s Republic of China.
