Global ablation of the mouse Rab11a gene impairs early embryogenesis and matrix metalloproteinase secretion

J Biol Chem. 2014 Nov 14;289(46):32030-32043. doi: 10.1074/jbc.M113.538223. Epub 2014 Sep 30.

Abstract

Rab11a has been conceived as a prominent regulatory component of the recycling endosome, which acts as a nexus in the endo- and exocytotic networks. The precise in vivo role of Rab11a in mouse embryonic development is unknown. We globally ablated Rab11a and examined the phenotypic and molecular outcomes in Rab11a(null) blastocysts and mouse embryonic fibroblasts. Using multiple trafficking assays and complementation analyses, we determined, among multiple important membrane-associated and soluble cargos, the critical contribution of Rab11a vesicular traffic to the secretion of multiple soluble MMPs. Rab11a(null) embryos were able to properly form normal blastocysts but died at peri-implantation stages. Our data suggest that Rab11a critically controls mouse blastocyst development and soluble matrix metalloproteinase secretion.

Keywords: Embryo; Matrix Metalloproteinase (MMP); Mouse Genetics; Rab; Rab11; Rab11a; Trafficking; rab11.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Alleles
  • Animals
  • Blastocyst / cytology
  • Embryonic Development
  • Female
  • Fibroblasts / cytology
  • Gene Expression Regulation, Developmental*
  • Genome
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 7 / metabolism
  • Matrix Metalloproteinases / metabolism*
  • Mice
  • Mice, Knockout
  • Pregnancy
  • Pregnancy, Animal
  • Transferrin / metabolism
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / physiology*

Substances

  • Transferrin
  • Alkaline Phosphatase
  • Matrix Metalloproteinases
  • Matrix Metalloproteinase 7
  • Matrix Metalloproteinase 2
  • Mmp2 protein, mouse
  • rab11 protein
  • rab GTP-Binding Proteins