Izumi Tetsuro, Gomi Hiroshi, Kasai Kazuo, Mizutani Shin, Torii Seiji
Department of Molecular Medicine, Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-machi, Maebashi, Gunma 371-8512, Japan.
Cell Struct Funct. 2003 Oct;28(5):465-74. doi: 10.1247/csf.28.465.
Regulated secretory pathways are highly developed in multicellular organisms as a means of intercellular communication. Each of these pathways harbors unique store organelles, such as granules in endocrine and exocrine tissues and melanosomes in melanocytes. It has recently been shown that the monomeric GTPase Rab27 subfamily regulates the exocytosis of these cell-specific store organelles. Furthermore, genetic alterations of Rab27a cause Griscelli syndrome in humans that manifests as pigmentary dilution of the skin and the hair and variable immunodeficiency due to defects in the transport of melanosomes in melanocytes and lytic granules in cytotoxic T-lymphocytes. Rab27 acts through organelle-specific effector proteins, such as granuphilin in pancreatic beta cells and melanophilin in melanocytes. The Rab27 and effector complex then interacts with proteins that are essential for membrane transport and fusion, such as syntaxin 1a and Munc18-1 for granuphilin and myosin Va for melanophilin. Genome information suggests that other putative Rab27 effector proteins, tentatively termed as exophilins or Slp/Slac2, are predicted to exist because these proteins share the conserved N-terminal Rab27-binding domain and show Rab27-binding activity in vitro or when overexpressed in cell lines. These findings suggest that the Rab27 subfamily regulates various exocytotic pathways using multiple organelle-specific effector proteins.
调节性分泌途径在多细胞生物中高度发达，是一种细胞间通讯方式。这些途径中的每一条都含有独特的储存细胞器，如内分泌和外分泌组织中的颗粒以及黑素细胞中的黑素体。最近的研究表明，单体GTP酶Rab27亚家族调节这些细胞特异性储存细胞器的胞吐作用。此外，Rab27a的基因改变会导致人类发生格里塞利综合征，表现为皮肤和毛发色素稀释，以及由于黑素细胞中黑素体和细胞毒性T淋巴细胞中溶酶体颗粒运输缺陷导致的可变免疫缺陷。Rab27通过细胞器特异性效应蛋白发挥作用，如胰腺β细胞中的颗粒亲和素和黑素细胞中的黑素亲和素。然后，Rab27与效应复合物与膜运输和融合所必需的蛋白质相互作用，如颗粒亲和素的 syntaxin 1a和Munc18-1，以及黑素亲和素的肌球蛋白Va。基因组信息表明，预计还存在其他假定的Rab27效应蛋白，暂称为外亲蛋白或Slp/Slac2，因为这些蛋白共享保守的N端Rab27结合结构域，并在体外或在细胞系中过表达时显示Rab27结合活性。这些发现表明，Rab27亚家族利用多种细胞器特异性效应蛋白调节各种胞吐途径。
