Korobko E V, Kiselev S L, Korobko I V
Institute of Gene Biology, Russian Academy of Sciences, Moscow, 119334, Russia.
Biochemistry (Mosc). 2014 Sep;79(9):856-64. doi: 10.1134/S000629791409003X.
Rab GTPases are key regulators of intracellular membrane traffic acting through their effector molecules. Rabaptin-5 is a Rab5 effector in early endosome fusion and connects Rab5- and Rab4-positive membrane compartments owing to its ability to interact with Rab4 GTPase. Recent studies showed that Rabaptin-5 transcript is subjected to extensive alternative splicing, thus resulting in expression of Rabaptin-5 isoforms mostly bearing short deletions in the polypeptide chain. As interactions of a Rab GTPase with different effectors lead to different responses, functional characterization of Rabaptin-5 isoforms becomes an attractive issue. Indeed, it was shown that Rab GTPase effector properties of Rabaptin-5 and its α and δ isoforms are different. This work focused on another Rabaptin-5 isoform, Rabaptin-5γ. Despite its ability to interact with Rab5, endogenously produced Rabaptin-5γ was absent from early endosomes. Rather, it was found to be tightly associated with trans-Golgi network and partially localized to a Rab4-positive membrane compartment. The revealed intracellular localization of Rabaptin-5γ indicates that it is not involved in Rab5-driven events; rather, it functions in other membrane transport steps. Our study signifies the role of alternative splicing in determination of functional activities of Rab effector molecules.
Rab GTP酶是通过其效应分子发挥作用的细胞内膜运输的关键调节因子。Rabaptin-5是早期内体融合过程中的Rab5效应分子，由于其能够与Rab4 GTP酶相互作用，从而连接Rab5和Rab4阳性的膜区室。最近的研究表明，Rabaptin-5转录本会发生广泛的可变剪接，从而导致Rabaptin-5异构体的表达，这些异构体在多肽链中大多带有短缺失。由于Rab GTP酶与不同效应分子的相互作用会导致不同的反应，因此Rabaptin-5异构体的功能特性成为一个引人关注的问题。事实上，已表明Rabaptin-5及其α和δ异构体的Rab GTP酶效应特性是不同的。这项工作聚焦于另一种Rabaptin-5异构体Rabaptin-5γ。尽管它能够与Rab5相互作用，但早期内体中不存在内源性产生的Rabaptin-5γ。相反，发现它与反式高尔基体网络紧密相关，并部分定位于Rab4阳性的膜区室。所揭示的Rabaptin-5γ的细胞内定位表明它不参与Rab5驱动的事件；相反，它在其他膜运输步骤中发挥作用。我们的研究表明了可变剪接在确定Rab效应分子功能活性中的作用。
