Katayama Taiichi, Imaizumi Kazunori, Yoneda Takunari, Taniguchi Manabu, Honda Akiko, Manabe Takayuki, Hitomi Junichi, Oono Kayoko, Baba Kousuke, Miyata Shingo, Matsuzaki Shinsuke, Takatsuji Koichi, Tohyama Masaya
Department of Anatony & Neuroscience, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
Cell Mol Neurobiol. 2004 Feb;24(1):137-47. doi: 10.1023/b:cemn.0000012719.12015.ec.
The human ADP-ribosylation factor-like protein, ARF4L is a member of the ARF family, which are small GTP-binding proteins that play significant roles in vesicle transport and protein secretion. However, little is known about the physiological roles of ARF4L. In this study, to understand the biological functions of ARF4L, we carried out immunocytochemical analysis of ARF4L molecules with mutations in the functional domains. ARF4L was shown to be distributed to the plasma membrane following binding to GTP (Q80L), and into endosomes following binding to GDP (T35N). Moreover, the inactive-form of ARF4L (T35N) causes localization of transferrin receptors to the endosomal compartment, while the active form (Q80L) causes transport to the plasma membrane. These findings indicate that ARF4L drive the transport of cargo protein and subsequent fusion of recycling vesicles with the plasma membrane for maintenance of the cell surface.
人类ADP核糖基化因子样蛋白ARF4L是ARF家族的成员,ARF家族是一类小的GTP结合蛋白,在囊泡运输和蛋白质分泌中发挥重要作用。然而,人们对ARF4L的生理作用知之甚少。在本研究中,为了了解ARF4L的生物学功能,我们对功能域发生突变的ARF4L分子进行了免疫细胞化学分析。结果显示,ARF4L在与GTP结合(Q80L)后分布于质膜,在与GDP结合(T35N)后进入内体。此外,ARF4L的无活性形式(T35N)导致转铁蛋白受体定位于内体区室,而活性形式(Q80L)则导致其转运至质膜。这些发现表明,ARF4L驱动货物蛋白的运输以及回收囊泡随后与质膜的融合,以维持细胞表面。