title: Phenotypic characterisation of RAB6A knockout mouse embryonic fibroblasts.
abstract: BACKGROUND
  Rab6 is one of the most conserved Rab GTPaes throughout evolution and the most abundant Rab protein associated with the Golgi complex. The two ubiquitous Rab isoforms, Rab6A and Rab6A', that are generated by alternative splicing of the RAB6A gene, regulate several transport steps at the Golgi level, including retrograde transport between endosomes and Golgi, anterograde transport between Golgi and the plasma membrane, and intra-Golgi and Golgi to endoplasmic reticulum transport.
  
  
  RESULTS
  We have generated mice with a conditional null allele of RAB6A. Mice homozygous for the RAB6A null allele died at an early stage of embryonic development. Mouse embryonic fibroblasts (MEFs) were isolated from RAB6A(loxP/loxP) Rosa26-CreERT2 and incubated with 4-hydroxy tamoxifen, resulting in the efficient depletion of Rab6A and Rab6A'. We show that Rab6 depletion affects cell growth, alters Golgi morphology and decreases the Golgi-associated levels of some known Rab6 effectors such as Bicaudal-D and myosin II. We also show that Rab6 depletion protects MEFs against ricin toxin and delays VSV-G secretion.
  
  
  CONCLUSIONS
  Our study shows that RAB6 is an essential gene required for normal embryonic development. We confirm in MEF cells most of the functions previously attributed to the two ubiquitous Rab6 isoforms.
authors: Institut Curie, PSL Research University and CNRS UMR 144, Paris, 75248, France.
authors: Sabine
authors: S
authors: Bardin
authors: Institut Curie, PSL Research University and CNRS UMR 144, Paris, 75248, France.
authors: Stéphanie
authors: S
authors: Miserey-Lenkei
authors: Institut Curie, PSL Research University and CNRS UMR 144, Paris, 75248, France.
authors: Ilse
authors: I
authors: Hurbain
authors: Institut Curie, PSL Research University, CNRS UMR 3666 and INSERM U1143, Paris, 75248, France.
authors: Daniela
authors: D
authors: Garcia-Castillo
authors: Institut Curie, PSL Research University and CNRS UMR 144, Paris, 75248, France.
authors: Graça
authors: G
authors: Raposo
authors: Institut Curie, PSL Research University and CNRS UMR 144, Paris, 75248, France.
authors: Bruno
authors: B
authors: Goud
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000235:genetics; D047108:Embryonic Development / Q000235:genetics*; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D012276:Ricin / Q000633:toxicity; D013629:Tamoxifen / Q000008:administration & dosage; D020691:rab GTP-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*
chemical_list: C094135:Rab6 protein; D013629:Tamoxifen; D012276:Ricin; D020691:rab GTP-Binding Proteins
keywords: Endocytosis/exocytosis; Endoplasmic reticulum/Golgi; Membrane transport