Non-canonical functions of the V-ATPase and their disease implications
The vacuolar H+ ATPase (V-ATPase) is an ATP dependent proton pump localized to the endomembrane system of all eukaryotic cells, where it acidifies intracellular compartments. As such, the V-ATPase maintains optimum organellar pH for their respective functions. Acidification by the V-ATPase is required for basic cellular functions such as pH and ion homeostasis, endocytosis, protein degradation, hormone secretion, neurotransmitter uptake and pathogen entry. Aberration in V-ATPase's proton pumping activity is associated with diseases of the kidney and bone, deafness, diabetes and cancer, with complete abrogation resulting in embryonic lethality.
The V-ATPase is a multisubunit, membrane protein complex which works as a rotary molecular motor and years of structural and biochemical investigation has delineated the enzyme's mechanism to a significant extent. Recently, the V-ATPase has emerged as a protein-protein interaction hub with functional involvement in metabolic signaling, autophagy, immune response and embryonic development. These non-canonical functions of the V-ATPase have implications in neurodegenerative diseases and cancer. The V-ATPase is a large and conformationally dynamic motor complex and understanding how this molecular machine accomplishes multiple roles will be the overarching goal of our lab.
To learn more about our research, email us at email@example.com