Rab27b regulates mast cell granule dynamics and secretion.
Rab27b regulates mast cell granule dynamics and secretion.
复制标题
RAB27B调节肥大细胞颗粒动力学和分泌。
DOI：
10.1111/j.1600-0854.2007.00571.x
复制
发表时间：
2007-07
期刊：
影响因子：
4.5
通讯作者：
Seabra, Miguel C
中科院分区：
文献类型：
--
作者：
Mizuno, Kouichi;Tolmachova, Tanya;Ushakov, Dmitry S;Romao, Maryse;Abrink, Magnus;Ferenczi, Michael A;Raposo, Graca;Seabra, Miguel C
Rab GT3家族调节膜结构域组织和囊泡转运途径。最近的研究表明，Rab 27 a家族的一个成员，调节特殊细胞中溶酶体相关细胞器的转运，如黑素体和溶解颗粒。关于Rab 27 b的相关亚型知之甚少。在这里，我们使用转基因小鼠来研究Rab 27蛋白在肥大细胞中的参与，肥大细胞在过敏反应中起关键作用。Rab 27 a和Rab 27 b亚型均在骨髓源性肥大细胞（BMMC）中表达，并定位于分泌颗粒。然而，通过体外β-氨基己糖苷酶释放和体内被动皮肤过敏反应测量的分泌缺陷仅在Rab 27 b和双Rab 27敲除（KO）小鼠中发现。免疫荧光研究表明，Rab 27 b和双Rab 27缺陷BMMC的子集表现出轻微的颗粒聚集。活细胞延时成像的定量分析显示，来自双Rab 27 KO小鼠的BMMC显示出几乎10倍的颗粒增加，表现出快速运动（>1.5 μm/s），这可以被诺考达唑破坏。这些结果表明，Rab 27蛋白，特别是Rab 27 b，在肥大细胞脱粒中起着至关重要的作用，它们的作用调节从微管到肌动蛋白为基础的运动的过渡。
The Rab GTPase family regulates membrane domain organization and vesicular transport pathways. Recent studies indicate that one member of the family, Rab27a, regulates transport of lysosome-related organelles in specialized cells, such as melanosomes and lytic granules. Very little is known about the related isoform, Rab27b. Here we used genetically modified mice to study the involvement of the Rab27 proteins in mast cells, which play key roles in allergic responses. Both Rab27a and Rab27b isoforms are expressed in bone marrow-derived mast cells (BMMC) and localize to secretory granules. Nevertheless, secretory defects as measured by β-hexosaminidase release in vitro and passive cutaneous anaphylaxis in vivo were found only in Rab27b and double Rab27 knockout (KO) mice. Immunofluorescence studies suggest that a subset of Rab27b and double Rab27-deficient BMMCs exhibit mild clustering of granules. Quantitative analysis of live-cell time-lapse imaging revealed that BMMCs derived from double Rab27 KO mice showed almost 10-fold increase in granules exhibiting fast movement (>1.5 μm/s), which could be disrupted by nocodazole. These results suggest that Rab27 proteins, particularly Rab27b, play a crucial role in mast cell degranulation and that their action regulates the transition from microtubule to actin-based motility.