過敏癥或者說免疫系統(tǒng)的超敏反應(yīng)如今越來越常見,。根據(jù)美國(guó)哮喘與過敏癥基金會(huì)的統(tǒng)計(jì),，每5個(gè)美國(guó)人中就1人患上過敏癥，癥狀從較為溫和的類型(如枯草熱)到更加嚴(yán)重的類型,，如能夠?qū)е逻^敏性休克(anaphylactic shock)產(chǎn)生的花生過敏,。以色列特拉維夫大學(xué)賽克勒醫(yī)學(xué)院(Tel Aviv University's Sackler Faculty of Medicine)細(xì)胞生物學(xué)者Ronit Sagi-Eisenberg教授和她的同事們正在努力鑒定出是什么觸發(fā)身體產(chǎn)生過敏反應(yīng)，以便最終在過敏反應(yīng)發(fā)生之前阻止它產(chǎn)生,。
答案可能就在Rab蛋白家族,，是由已知調(diào)節(jié)蛋白在全身分布的60種蛋白組成的家族。Sagi-Eisenberg教授與博士生Nurit Pereg-Azouz一起通過基因操縱肥大細(xì)胞而讓這些細(xì)胞含有Rab蛋白家族成員的突變體,。如果一種是比較相關(guān)的話,，它將導(dǎo)致過敏反應(yīng)。利用這種方法允許研究人員篩選這種蛋白家族中每個(gè)成員的功能性影響,，以便確定它們是否抑制或激活過敏反應(yīng),。
研究人員發(fā)現(xiàn)這些蛋白中的30種確定細(xì)胞如何對(duì)過敏原作出反應(yīng)，而且鑒定出它們中的兩種可用于開發(fā)出預(yù)防性藥物研究,。Sagi-Eisenberg教授說,，當(dāng)導(dǎo)致過敏反應(yīng)的一連串事件能夠被理解時(shí)，人們就能夠開發(fā)藥物來抑制初始反應(yīng),。相關(guān)研究發(fā)表在Journal of Immunology期刊上,。(生物谷：Bioon.com)
本文編譯自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.
