The R740S mutation in the V-ATPase a3 subunit results in osteoclast apoptosis and defective early-stage autophagy.

Abstract excerpt

Vacuolar-type H(+)-ATPases (V-ATPases) are located in lysosomes and at the ruffled border in osteoclasts. We showed previously that the R740S mutation is dominant negative for V-ATPase activity, uncouples proton transport from ATP hydrolysis and causes osteopetrosis in heterozygous mice (+/R740S). Here we show mice homozygous for R740S (R740S/R740S) have more severe osteopetrosis and die by postnatal day 14....

Topics

• Animals
• Apoptosis
• Autophagy
• Cell Differentiation
• Cytoplasm
• Lysosomes
• Mice
• Mutation
• Osteoclasts
• Osteopetrosis
• Protein Subunits
• Vacuolar Proton-Translocating ATPases