The TGF-β signaling modulators TRAP1/TGFBRAP1 and VPS39/Vam6/TLP are essential for early embryonic development.
The pleiotropic cytokine transforming growth factor-β (TGF-β) signals through different pathways among which the Smad- and the MAP-Kinase pathways are already well characterized. Both pathways utilize adaptor/chaperone molecules that facilitate or modulate the intracellular signaling events. Two of the proteins shown in vitro to play a role in Smad-dependent signaling are the TGF-β Receptor Associated Protein-1 (TRAP1, also TGFBRAP1) and its homologue VPS39, also known as Vam6 and TRAP1-Like-Protein (TLP). We generated mice deficient for TRAP1 and VPS39/TLP, respectively. Absence of TRAP1 protein results in death at either of two defined timepoints during embryogenesis, before the blastula stage or during gastrulation, whereas most of the VPS39 deficient mice die before E6.5. Heterozygous mice show no overt phenotype. In summary, our data indicate that TRAP1 and VPS39 are nonredundant and essentially required for early embryonic development.
Institute for Medical Microbiology and Hospital Hygiene, University of Duesseldorf, 40225 Duesseldorf, Germany.
Sabine
S
Messler
Sonja
S
Kropp
Vasso
V
Episkopou
Angelina
A
Felici
Jan
J
Würthner
Robin
R
Lemke
Moran
M
Jerabek-Willemsen
Regina
R
Willecke
Stefanie
S
Scheu
Klaus
K
Pfeffer
Jens U
JU
Wurthner
D000818:Animals; D030801:Animals, Genetically Modified; D000071183:Autophagy-Related Proteins; D036703:Blastula / Q000196:embryology*; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D047108:Embryonic Development; D005775:Gastrula / Q000196:embryology*; D015870:Gene Expression; D005838:Genotype; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D016133:Polymerase Chain Reaction; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D033921:Vesicular Transport Proteins
D000071183:Autophagy-Related Proteins; D020662:Guanine Nucleotide Exchange Factors; D018841:HSP90 Heat-Shock Proteins; D047908:Intracellular Signaling Peptides and Proteins; C547760:TRAP-1 protein, mouse; D016212:Transforming Growth Factor beta; C550074:VPS39 protein, mouse; D033921:Vesicular Transport Proteins