Department of Dental Pharmacology, Graduate School of Biomedical Sciences, Nagasaki University, Sakamoto 1-7-1, Nagasaki 852-8588, Japan.
Department of Frontier Oral Science, Graduate School of Biomedical Sciences, Nagasaki University, Sakamoto 1-7-1, Nagasaki 852-8588, Japan.
Int J Mol Sci. 2021 Jul 19;22(14):7691. doi: 10.3390/ijms22147691.
Rab GTPases are major coordinators of intracellular membrane trafficking, including vesicle transport, membrane fission, tethering, docking, and fusion events. Rab GTPases are roughly divided into two groups: conventional "small" Rab GTPases and atypical "large" Rab GTPases that have been recently reported. Some members of large Rab GTPases in mammals include Rab44, Rab45/RASEF, and Rab46. The genes of these large Rab GTPases commonly encode an amino-terminal EF-hand domain, coiled-coil domain, and the carboxyl-terminal Rab GTPase domain. A common feature of large Rab GTPases is that they express several isoforms in cells. For instance, Rab44's two isoforms have similar functions, but exhibit differential localization. The long form of Rab45 (Rab45-L) is abundantly distributed in epithelial cells. The short form of Rab45 (Rab45-S) is predominantly present in the testes. Both Rab46 (CRACR2A-L) and the short isoform lacking the Rab domain (CRACR2A-S) are expressed in T cells, whereas Rab46 is only distributed in endothelial cells. Although evidence regarding the function of large Rab GTPases has been accumulating recently, there are only a limited number of studies. Here, we report the recent findings on the large Rab GTPase family concerning their function in membrane trafficking, cell differentiation, related diseases, and knockout mouse phenotypes.
Rab GTPases 是细胞内膜运输的主要协调因子，包括囊泡运输、膜裂变、连接、对接和融合事件。Rab GTPases 大致可分为两类：传统的“小”Rab GTPases 和最近报道的非典型“大”Rab GTPases。哺乳动物中一些大 Rab GTPases 的成员包括 Rab44、Rab45/RASEF 和 Rab46。这些大 Rab GTPases 的基因通常编码一个氨基末端 EF 手结构域、卷曲螺旋结构域和羧基末端 Rab GTPase 结构域。大 Rab GTPases 的一个共同特征是它们在细胞中表达几种同工型。例如，Rab44 的两种同工型具有相似的功能，但表现出不同的定位。Rab45 的长形式（Rab45-L）在上皮细胞中大量分布。Rab45 的短形式（Rab45-S）主要存在于睾丸中。Rab46（CRACR2A-L）和缺乏 Rab 结构域的短同工型（CRACR2A-S）都在 T 细胞中表达，而 Rab46 仅分布在内皮细胞中。尽管最近关于大 Rab GTPases 功能的证据不断增加，但研究数量有限。在这里，我们报告了大 Rab GTPase 家族在膜运输、细胞分化、相关疾病和敲除小鼠表型方面的最新研究结果。
