Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
Department of Dermatology, Yonsei University College of Medicine, Seoul, Korea.
FASEB J. 2018 Feb;32(2):957-968. doi: 10.1096/fj.201700563R. Epub 2018 Jan 4.
Microtubule-based motors contribute to the efficiency and selectivity of Golgi exit and post-Golgi transport of membrane proteins that are targeted to distinct compartments. Cytoplasmic dynein moves post-Golgi vesicles that carry rhodopsin toward the base of the connecting cilium in photoreceptor cells; however, the identity of the motors that are involved in the vesicular trafficking of ciliary membrane proteins in nonphotoreceptor cells remains unclear. Here, we demonstrate that the minus end-directed kinesin KIFC1 (kinesin family member C1) is required for both ciliary membrane protein transport and serum starvation-induced ciliogenesis in retinal pigmented epithelial 1 cells. Although KIFC1 is known as a mitotic motor that is sequestered in the nucleus during interphase, KIFC1 immunoreactivity appeared in the Golgi region after serum starvation. Knockdown of KIFC1 inhibited the export of ciliary receptors from the Golgi complex. KIFC1 overexpression affected the Golgi localization of GMAP210 (Golgi microtubule-associated protein 210) and IFT20 (intraflagellar transport 20), which are involved in membrane protein transport to cilia. Moreover, KIFC1 physically interacted with ASAP1 (ADP-ribosylation factor GTPase-activating protein with SH3 domain, ankyrin repeat and PH domain 1), which regulates the budding of rhodopsin transport carriers from the Golgi complex, and KIFC1 depletion caused Golgi accumulation of ASAP1. A decrease in the centrosomal levels of IFT20 and TTBK2 (τ-tubulin kinase 2) was associated with ciliogenesis defects in KIFC1-depleted cells. Our results suggest that KIFC1 plays roles in the Golgi exit of ciliary receptors and in the recruitment of ciliogenesis regulators.-Lee, S.-H., Joo, K., Jung, E. J., Hong, H., Seo, J., Kim, J. Export of membrane proteins from the Golgi complex to the primary cilium requires the kinesin motor, KIFC1.
微管动力蛋白有助于高尔基体出口的效率和选择性，以及靶向不同隔室的膜蛋白的高尔基体后运输。细胞质动力蛋白使携带视紫红质的高尔基后期小泡向感光细胞连接纤毛的基部移动;然而，参与非感光细胞中纤毛膜蛋白囊泡运输的动力蛋白的身份尚不清楚。在这里，我们证明负向导向的驱动蛋白 KIFC1（驱动蛋白家族成员 C1）对于视网膜色素上皮 1 细胞的纤毛膜蛋白运输和血清饥饿诱导的纤毛发生都是必需的。尽管 KIFC1 是一种有丝分裂驱动蛋白，在细胞间期中被隔离在核内，但在血清饥饿后，KIFC1 免疫反应性出现在高尔基区。KIFC1 的敲低抑制了纤毛受体从高尔基复合体的输出。KIFC1 的过表达影响 GMAP210（高尔基微管相关蛋白 210）和 IFT20（鞭毛内运输 20）的高尔基定位，这两者都参与了膜蛋白向纤毛的运输。此外，KIFC1 与 ASAP1（ADP-核糖基化因子 GTP 酶激活蛋白具有 SH3 结构域、锚蛋白重复和 PH 结构域 1）发生物理相互作用，ASAP1 调节视紫红质运输载体从高尔基复合体的出芽，KIFC1 的耗竭导致 ASAP1 在高尔基复合体中的积累。IFT20 和 TTBK2（τ-微管蛋白激酶 2）中心体水平的降低与 KIFC1 耗尽细胞中的纤毛发生缺陷有关。我们的结果表明，KIFC1 在高尔基出口的纤毛受体和招募纤毛发生调节剂中发挥作用。-李，S.-H.，Joo，K.，Jung，E. J.，Hong，H.，Seo，J.，Kim，J. 膜蛋白从高尔基体复合物到初级纤毛的输出需要驱动蛋白 KIFC1。
