Rab27b is expressed in a wide range of exocytic cells and involved in the delivery of secretory granules near the plasma membrane
Rab27b is expressed in a wide range of exocytic cells and involved in the delivery of secretory granules near the plasma membrane
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DOI：
10.1091/mbc.e07-05-0409
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发表时间：
2007-11-01
影响因子：
3.3
通讯作者：
Izumi, Tetsuro
中科院分区：
文献类型：
--
作者：
Gomi, Hiroshi;Mori, Kenichi;Izumi, Tetsuro
Rab蛋白调节膜运输的多个复杂过程。在这些蛋白质中，Rab 27 a已被证明在受调节的胞吐途径中特异性地起作用。然而，Rab 27亚家族的另一个成员Rab 27 b的作用还没有得到很好的表征。我们破坏了小鼠的Rab 27 b基因。设计靶向载体以将LacZ插入Rab 27 b基因的起始密码子下游，使得真实启动子应当驱动该报告基因。使用该小鼠品系对Rab 27 b表达的综合分析表明，它不仅在典型分泌细胞中广泛表达，而且在参与表面保护和机械延伸的神经元和细胞中也广泛表达。为了评估在垂体内分泌细胞中Rab 27 a亚型共表达的功能，我们通过将Rab 27 b敲除小鼠与Rab 27 a突变的灰鼠杂交来产生Rab 27 a/Rab 27 b双敲除小鼠。在双基因敲除小鼠的垂体中，靠近质膜的分泌颗粒的极化分布明显受损，这表明Rab 27亚家族参与了胞外部位附近颗粒的递送。结合具有垂体缺乏Rab 27效应颗粒亲蛋白的表型，我们讨论了居住和颗粒的可释放池之间的关系。
Rab proteins regulate multiple, complex processes of membrane traffic. Among these proteins, Rab27a has been shown to function specifically in regulated exocytic pathways. However, the roles of Rab27b, another Rab27 subfamily member, have not been well characterized. We disrupted the Rab27b gene in mice. The targeting vector was designed to insert LacZ downstream of the initiation codon of the Rab27b gene so that the authentic promoter should drive this reporter gene. A comprehensive analysis of Rab27b expression using this mouse strain indicated that it is widely expressed not only in canonical secretory cells, but also in neurons and cells involved in surface protection and mechanical extension. To evaluate the function in pituitary endocrine cells where the isoform Rab27a is coexpressed, we generated Rab27a/Rab27b double knockout mice by crossing Rab27b knockout mice with Rab27a-mutated ashen mice. The polarized distribution of secretory granules close to the plasma membrane was markedly impaired in the pituitary of double knockout mice, indicating that the Rab27 subfamily is involved in the delivery of granules near the exocytic site. In conjunction with a phenotype having a pituitary devoid of the Rab27 effector granuphilin, we discuss the relationship between the residence and the releasable pool of granules.