KIF16B/Rab14 molecular motor complex is critical for early embryonic development by transporting FGF receptor.
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.
Department of Cell Biology and Anatomy, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Hitoshi
H
Ueno
Xiao
X
Huang
Yosuke
Y
Tanaka
Nobutaka
N
Hirokawa
D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D019070:Cell Lineage; D002462:Cell Membrane / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D058732:Embryoid Bodies / Q000166:cytology / Q000378:metabolism; D047108:Embryonic Development; D004707:Endoderm / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D006801:Humans; D016547:Kinesins / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D011485:Protein Binding; D021381:Protein Transport; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000378:metabolism*; D015398:Signal Transduction; D022161:Transport Vesicles / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000378:metabolism*
C496354:Fgfr2 protein, mouse; D051497:Receptor, Fibroblast Growth Factor, Type 2; C555882:Rab14 protein, mouse; C555883:kinesin family member 16B; D016547:Kinesins; D020691:rab GTP-Binding Proteins