oligomycins and Alkalosis

1. In order to investigate the biological function of the human CLN3 gene that is defective in Batten disease, we created a yeast strain by PCR-targeted disruption of the yeast gene (YHC3), which is a homologue of the human CLN3 gene. 2. The phenotypic characterization revealed that the yhc3 delta mutants are more sensitive to combined heat and alkaline stress than the wild-type strains as determined by inhibition of cell proliferation. 3. This suggests that the yhc3 delta mutant is a good model to investigate the biological function of human CLN3 gene in mammalian cells and to understand the pathophysiology of juvenile Batten disease.

Topics: Alkalosis; Antineoplastic Agents; Cyclins; Enzyme Inhibitors; Humans; Hydrogen-Ion Concentration; Membrane Glycoproteins; Molecular Chaperones; Neuronal Ceroid-Lipofuscinoses; Oligomycins; Proteins; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins

We have shown elsewhere that membranes isolated from the turtle bladder epithelium have both vanadate-resistant (VR) and vanadate-sensitive (VS) components of ATP-dependent H+ transport. VR appears to be due to a vacuolar-type H+ uniport while VS has properties of an H/K exchanger. In the present study we used bladders from chronically alkalotic turtles, which do not acidify urine, and found them to yield membranes which retain VR but lack VS transport. Thus VS occurs only in membranes from bladders secreting acid, implying that VS H+ transport (1) plays a physiological role in the secretion and (2) is a functional marker for the apical membrane of the acid-secreting cells. These results suggest a new model for distal urinary acidification.

Topics: Adenosine Triphosphate; Alkalosis; Animals; Cell Membrane; Epithelium; Hydrogen-Ion Concentration; In Vitro Techniques; Kinetics; Models, Biological; Oligomycins; Ouabain; Turtles; Urinary Bladder; Valinomycin; Vanadates