清華大學醫(yī)學院免疫學系,，第二軍醫(yī)大免疫研究所，醫(yī)學免疫國家重點實驗室的研究者在最新一期的The Journal of Immunology上發(fā)表免疫新發(fā)現,，文章標題：Human SCAMP5, a Novel Secretory Carrier Membrane Protein, Facilitates Calcium-Triggered Cytokine Secretion by Interaction with SNARE Machinery,。
免疫細胞分泌細胞因子是機體天然免疫和獲得性免疫的重要調節(jié)方式。然而,，免疫細胞如何分泌細胞因子調節(jié)免疫系統(tǒng)的機制一直不被人所知,。分泌載體膜蛋白（Secretory carrier membrane proteins，SCAMPs）廣泛存在與細胞囊泡運輸系統(tǒng)皺褶中的蛋白,。在本篇研究性文章中,，曹雪濤院士等人主要解析了人類分泌載體膜蛋白SCAMP5（hSCAMP5）的功能特征，SCAMP5是分泌載體膜蛋白的一種,，廣泛存在于神經組織和非神經組織細胞內,。
研究發(fā)現在人類上皮癌細胞、單核細胞和小鼠巨噬細胞中SCAMP5能促進鈣調節(jié)的信號肽細胞因子分泌（包括CCL5,，不包括IL-1β）,。研究人員用亞細胞結構分離技術，免疫熒光共聚焦顯微鏡檢測技術,，囊泡免疫分離技術,，對人SCAMP5研究發(fā)現其主要定位在高爾基體的間隔室內，鈣離子載體能促使hSCAMP5易位,，通過經典的細胞胞吐通道使其迅速從高爾基體轉移到細胞膜外,。
深入的研究發(fā)現hSCAMP5能與附著蛋白受體（attachment protein receptors，SNAREs）相互作用,，協(xié)助SNAREs參與改調節(jié)的胞吐作用,，調節(jié)信號肽和細胞因子的分泌,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
