A procedure has been developed that allows for the depletion of rat liver plasma membrane cholesterol by incubation with liposomes at 4 degrees C. Upon cholesterol depletion, adenylate cyclase activity was inhibited and the membranes became more rigid, as determined by the flexibility of an incorporated fatty acid spin probe. Decreasing the cholesterol/phospholipid molar ratio elicited a pronounced drop in the net fold-stimulation of adenylate cyclase activity by glucagon. Two lipid phase separations were detected in cholesterol-depleted membranes at around 25 degrees C and 13 degrees C respectively. Breaks at these temperatures were observed in Arrhenius plots of both the mobility of the spin probe and the glucagon-stimulated adenylate cyclase activity for the range 2-40 degrees C, but only the one at the lower temperature for the fluoride-stimulated activity. It is proposed that the lipid phase separation occurring at 25 degrees C is localized in the external half of the bilayer, whereas that at 13 degrees C is due to lipids in the inner half of the bilayer. Similar structural and functional perturbations were manifest if the cholesterol-complexing polyene antibiotic amphotericin B was added to native membranes. The mechanism of adenylate cyclase inhibition achieved by cholesterol depletion and the domain structure of the plasma membrane in relation to cholesterol distribution are discussed. Native cholesterol/phospholipid ratios appear to optimize the functioning of adenylate cyclase in liver plasma membranes.
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May 1983
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Research Article|
May 15 1983
Adenylate cyclase is inhibited upon depletion of plasma-membrane cholesterol Available to Purchase
Publisher: Portland Press Ltd
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 1983 London: The Biochemical Society
1983
Biochem J (1983) 212 (2): 331–338.
Citation
A D Whetton, L M Gordon, M D Houslay; Adenylate cyclase is inhibited upon depletion of plasma-membrane cholesterol. Biochem J 15 May 1983; 212 (2): 331–338. doi: https://doi.org/10.1042/bj2120331
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