J Immunol：鉴定出一组可能触发过敏反应产生的蛋白

过敏症或者说免疫系统的超敏反应如今越来越常见。根据美国哮喘与过敏症基金会的统计，每5个美国人中就1人患上过敏症，症状从较为温和的类型(如枯草热)到更加严重的类型，如能够导致过敏性休克(anaphylactic shock)产生的花生过敏。以色列特拉维夫大学赛克勒医学院(Tel Aviv University's Sackler Faculty of Medicine)细胞生物学者Ronit Sagi-Eisenberg教授和她的同事们正在努力鉴定出是什么触发身体产生过敏反应，以便最终在过敏反应发生之前阻止它产生。

答案可能就在Rab蛋白家族，是由已知调节蛋白在全身分布的60种蛋白组成的家族。Sagi-Eisenberg教授与博士生Nurit Pereg-Azouz一起通过基因操纵肥大细胞而让这些细胞含有Rab蛋白家族成员的突变体。如果一种是比较相关的话，它将导致过敏反应。利用这种方法允许研究人员筛选这种蛋白家族中每个成员的功能性影响，以便确定它们是否抑制或激活过敏反应。

研究人员发现这些蛋白中的30种确定细胞如何对过敏原作出反应，而且鉴定出它们中的两种可用于开发出预防性药物研究。Sagi-Eisenberg教授说，当导致过敏反应的一连串事件能够被理解时，人们就能够开发药物来抑制初始反应。相关研究发表在Journal of Immunology期刊上。

本文编译自Research identifies a protein group that may kick-start allergic reactions

doi: 10.4049/jimmunol.1200542
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Decoding the Regulation of Mast Cell Exocytosis by Networks of Rab GTPases

Nurit P. Azouz*, Takahide Matsui†, Mitsunori Fukuda† and Ronit Sagi-Eisenberg

Exocytosis is a key event in mast cell functions. By this process, mast cells release inflammatory mediators, contained in secretory granules (SGs), which play important roles in immunity and wound healing but also provoke allergic and inflammatory responses. The mechanisms underlying mast cell exocytosis remained poorly understood. An essential step toward deciphering the mechanisms behind exocytosis is the identification of the cellular components that regulate this process. Because Rab GTPases regulate specific trafficking pathways, we screened 44 Rabs for their functional impacts on exocytosis triggered by the FcεRI or combination of Ca2+ ionophore and phorbol ester. Because exocytosis involves the continuous reorganization of the actin cytoskeleton, we also repeated our screen in the presence of cytochalasin D that inhibits actin polymerization. In this paper, we report on the identification of 30 Rabs as regulators of mast cell exocytosis, the involvement of 26 of which has heretofore not been recognized. Unexpectedly, these Rabs regulated exocytosis in a stimulus-dependent fashion, unless the actin skeleton was disrupted. Functional clustering of the identified Rabs suggested their classification as Rabs involved in SGs biogenesis or Rabs that control late steps of exocytosis. The latter could be further divided into Rabs that localize to the SGs and Rabs that regulate transport from the endocytic recycling compartment. Taken together, these findings unveil the Rab networks that control mast cell exocytosis and provide novel insights into their mechanisms of action.