Effect of mevalonate availability on the association of G-protein α-subunits with the plasma membrane in GH4C1 cells
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- 作者：Chiloeches ; Antonio ; Usera ; Fernado ; Lasa ; Marina ; Ropero ; Santiago ; Montes ; Agustí ; n ; et. al.
- 关键词：G-protein ; Adenylyl cyclase ; Mevalonate ; Cholesterol ; 25-Hydroxycholesterol
- 刊名：FEBS Letters
- 出版年：1997
- 出版时间：January 13, 1997
- 年：1997
- 卷：401
- 期：1
- 页码：68-72
- 全文大小：588 K
文摘
We show that the levels and activity of the α-subunits of Gs and Gi 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.