Effect of mevalonate availability on the association of G‐protein α‐subunits with the plasma membrane in GH4C1 cells

FEBS Letters

Toro, Marı́a J¹  Usera, Fernado¹  Lasa, Marina¹  Ropero, Santiago¹  Chiloeches, Antonio¹  Montes, Agustı́n² 

[1] Departamento de Bioquı́mica y Biologı́a Molecular, Universidad de Alcalá, Crta. Madrid-Barcelona Km. 33,6, 28871 Alcalá de Henares, Madrid, Spain;Departamento de Fisiologı́a y Farmacologı́a, Universidad de Alcalá, Crta. Madrid-Barcelona Km. 33,6, 28871 Alcalá de Henares, Madrid, Spain

关键词: G-protein;    Adenylyl cyclase;    Mevalonate;    Cholesterol;    25-Hydroxycholesterol;   

DOI  :  10.1016/S0014-5793(96)01434-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

We show that the levels and activity of the α-subunits of G_s and G_i proteins in plasma membrane of GH₄C₁ cells are regulated by the availability of mevalonate (MVA), and not by changes in cholesterol cell content. Changes in the levels of MVA, induced by modulation of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, determine the amount of both membrane-bound Gα-subunits, which correlated with the activity of their effector adenylyl cyclase. Lipoprotein deficient serum (LPDS) decreases cholesterol content and increases both HMG-CoA reductase activity and Gα-subunits in the membrane. Cholesterol and 25-hydroxycholesterol (25-HC) each repress HMG-CoA reductase and diminish Gα-subunit levels. However, while cholesterol cell content is also decreased by 25-HC, exogenous cholesterol increases it. In addition, the decrease of both Gα-subunits is reversed by the presence of MVA. This regulation appears to be mediated by nonsterol products generated from MVA. We assume that the first is the prenylation of the γ-subunits, since the attachment of Gα-subunits to the membrane is dependent on this modification. However, as neither of our treatments completely abolished protein prenylation, we conclude that another MVA derivative is required in addition to prenyl residues to the presence and activity of α-subunits in the membrane.

【 授权许可】

Unknown