KIF16B/Rab14 Molecular Motor Complex Is Critical for Early Embryonic Development by Transporting FGF Receptor
KIF16B/Rab14 Molecular Motor Complex Is Critical for Early Embryonic Development by Transporting FGF Receptor
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DOI：
10.1016/j.devcel.2010.11.008
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发表时间：
2011-01-18
影响因子：
11.8
通讯作者：
Hirokawa, Nobutaka
中科院分区：
文献类型：
--
作者：
Ueno, Hitoshi;Huang, Xiao;Hirokawa, Nobutaka
驱动蛋白介导的膜运输是一个基本的细胞过程，但其发育相关性知之甚少。在这里，我们表明，驱动蛋白-3电机KIF 16 B/Rab 14复杂的行为在生物合成高尔基体到内体交通的成纤维细胞生长因子受体（FGFR）在早期胚胎发育。Kif 16 b（-/-）小鼠胚胎未能发育成外胚层和原始内胚层谱系，并在笔植入阶段死亡，类似于先前报道的FGFR 2敲除胚胎。KIF 16 B直接与含有FGFR的囊泡上的Rab 14-GTP衔接子结合，并将其转运至质膜。为了检查Rab 14的核苷酸状态是否作为转运的开关，我们进行了Rab 14-GDP过表达。这种显性负性方法再现了KIF 16 B或FGFR 2缺陷的整个假定序列：FGFR转运、FGF信号传导、原始内胚层谱系的基底膜组装和上胚层发育受损。这些数据提供了第一批遗传证据之一，即基于微管的膜运输直接促进早期发育。
Kinesin-mediated membrane trafficking is a fundamental cellular process, but its developmental relevance is little understood. Here we show that the kinesin-3 motor KIF16B/Rab14 complex acts in biosynthetic Golgi-to-endosome traffic of the fibroblast growth factor receptor (FGFR) during early embryonic development. Kif16b(-/-) mouse embryos failed in developing epiblast and primitive endoderm lineages and died in the pen-implantation stage, similar to previously reported FGFR2 knockout embryos. KIF16B associated directly with the Rab14-GTP adaptor on FGFR-containing vesicles and transported them toward the plasma membrane. To examine whether the nucleotide state of Rab14 serves as a switch for transport, we performed Rab14-GDP overexpression. This dominant negative approach reproduced the whole putative sequence of KIF16B or FGFR2 deficiency: impairment in FGFR transport, FGF signaling, basement membrane assembly by the primitive endoderm lineage, and epiblast development. These data provide one of the first pieces of genetic evidence that microtubule-based membrane trafficking directly promotes early development.