KIF16B/Rab14 Molecular Motor Complex Is Critical for Early Embryonic Development by Transporting FGF Receptor

• Published in: Developmental cell 2011-01, Vol.20 (1), p.60-71
• Main Authors: Ueno, Hitoshi, Huang, Xiao, Tanaka, Yosuke, Hirokawa, Nobutaka
• Format: Article
• Language: English
• Subjects: Animals; Basement Membrane - metabolism; Biological and medical sciences; Cell differentiation, maturation, development, hematopoiesis; Cell Lineage; Cell Membrane - metabolism; Cell physiology; Cell receptors; Cell structures and functions; Embryo, Mammalian - cytology; Embryo, Mammalian - metabolism; Embryoid Bodies - cytology; Embryoid Bodies - metabolism; Embryonic Development; Endoderm - cytology; Endoderm - embryology; Endoderm - metabolism; Fundamental and applied biological sciences. Psychology; Humans; Kinesin - deficiency; Kinesin - metabolism; Mice; Miscellaneous; Molecular and cellular biology; Protein Binding; Protein Transport; rab GTP-Binding Proteins - metabolism; Receptor, Fibroblast Growth Factor, Type 2 - metabolism; Signal Transduction; Transport Vesicles - metabolism
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2010.11.008

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 peri-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. [Display omitted] ► Developmental phenotypes of KIF16B-deficient embryos and EBs mimic FGFR2 deficiency ► KIF16B transports FGFR2-containing vesicles toward the plasma membrane ► The adaptor Rab14-GTP directly acts on KIF16B to facilitate FGFR2 Golgi-to-endosome traffic ► Dominant-negative Rab14 disrupts FGFR2 signaling and reproduces KIF16B-KO effects