KIF16B/Rab14 molecular motor complex is critical for early embryonic development by transporting FGF receptor

Dev Cell. 2011 Jan 18;20(1):60-71. doi: 10.1016/j.devcel.2010.11.008.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basement Membrane / metabolism
  • Cell Lineage
  • Cell Membrane / metabolism
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / metabolism
  • Embryoid Bodies / cytology
  • Embryoid Bodies / metabolism
  • Embryonic Development*
  • Endoderm / cytology
  • Endoderm / embryology
  • Endoderm / metabolism
  • Humans
  • Kinesin / deficiency
  • Kinesin / metabolism*
  • Mice
  • Protein Binding
  • Protein Transport
  • Receptor, Fibroblast Growth Factor, Type 2 / metabolism*
  • Signal Transduction
  • Transport Vesicles / metabolism
  • rab GTP-Binding Proteins / metabolism*

Substances

  • Fgfr2 protein, mouse
  • Receptor, Fibroblast Growth Factor, Type 2
  • Rab14 protein, mouse
  • kinesin family member 16B
  • Kinesin
  • rab GTP-Binding Proteins