Physiological implications of the regulation of vacuolar H+-ATPase by chloride ions

Vacuolar H+-ATPase is a large multi-subunit protein that mediates ATP-driven vectorial H+ transport across the membranes. It is widely distributed and present in virtually all eukaryotic cells in intracellular membranes or in the plasma membrane of specialized cells. In subcellular organelles, ATPase is responsible for the acidification of the vesicular interior, which requires an intraorganellar acidic pH to maintain optimal enzyme activity. Control of vacuolar H+-ATPase depends on the potential difference across the membrane in which the proton ATPase is inserted. Since the transport performed by H+-ATPase is electrogenic, translocation of H+-ions across the membranes by the pump creates a lumen-positive voltage in the absence of a neutralizing current, generating an electrochemical potential gradient that limits the activity of H+-ATPase. In many intracellular organelles and cell plasma membranes, this potential difference established by the ATPase gradient is normally dissipated by a parallel and passive Cl- movement, which provides an electric shunt compensating for the positive charge transferred by the pump. The underlying mechanisms for the differences in the requirement for chloride by different tissues have not yet been adequately identified, and there is still some controversy as to the molecular identity of the associated Cl--conducting proteins. Several candidates have been identified: the ClC family members, which may or may not mediate nCl-/H+ exchange, and the cystic fibrosis transmembrane conductance regulator. In this review, we discuss some tissues where the association between H+-ATPase and chloride channels has been demonstrated and plays a relevant physiologic role.

Inhibition of avian myeloblastosis virus reverse transcriptase by an RNA-binding protein from plasma membranes of normal and tumor cells.

Purified plasma membranes from normal rat liver, a rat hepatoma and a rat hepatic fibrosarcoma have been shown to contain a protein which drastically inhibits avian myeloblastosis virus reverse transcriptase activity. The inhibition is caused by the binding of the protein to the template. The binding and the consequent inhibition of enzyme activity are template-specific; copying of RNA templates is inhibited whilst that of DNA templates remains unaffected. Investigations using different templates suggest that the inhibitory protein has a stronger binding affinity for G, C-rich templates. The inhibitor appears to have a wide distribution in plasma membranes from diverse sources.