Goishi Keiichi, Mizuno Kouichi, Nakanishi Hideki, Sasaki Takuya
Department of Biochemistry, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan.
Biochem Biophys Res Commun. 2004 Nov 5;324(1):294-301. doi: 10.1016/j.bbrc.2004.09.050.
The Rab family small G proteins regulate discrete steps in vesicular transport pathways. Recent studies indicate that one member of the Rab family, Rab27A, regulates the transport of lysosome-related organelles, such as melanosome distribution in melanocytes, lytic granule release in cytotoxic T cells, and dense granule release in platelets. Here, we have examined the involvement of Rab27A in the exocytic transport of another lysosome-related organelle, the basophilic secretory granule, in basophils. We have found that Rab27A locates on basophilic secretory granules containing histamine in rat basophilic leukemia (RBL) 2H3 cells. In addition, exogenous expression of dominant active Rab27A reduces antigen-induced histamine release from the cells. We have moreover identified Munc13-4 as a Rab27A target using a CytoTrap system and found that exogenous expression of Munc13-4 affects antigen-induced histamine release from RBL-2H3 cells. These results demonstrate that Rab27A plays a crucial role in antigen-induced histamine release from RBL-2H3 cells.
Rab家族小G蛋白调节囊泡运输途径中的不同步骤。最近的研究表明，Rab家族的一个成员Rab27A调节溶酶体相关细胞器的运输，如黑素细胞中黑素体的分布、细胞毒性T细胞中溶细胞颗粒的释放以及血小板中致密颗粒的释放。在这里，我们研究了Rab27A在嗜碱性粒细胞中另一种溶酶体相关细胞器——嗜碱性分泌颗粒的胞吐运输中的作用。我们发现Rab27A定位于大鼠嗜碱性白血病（RBL）2H3细胞中含有组胺的嗜碱性分泌颗粒上。此外，显性活性Rab27A的外源表达减少了抗原诱导的细胞组胺释放。我们还使用细胞陷阱系统鉴定出Munc13-4是Rab27A的一个靶点，并发现Munc13-4的外源表达影响抗原诱导的RBL-2H3细胞组胺释放。这些结果表明，Rab27A在抗原诱导的RBL-2H3细胞组胺释放中起关键作用。
