Sci. STKE, 27 February 2007
G Proteins G Protein-Mediated Inhibition of Autophagy
L. Bryan Ray
Science, Sciences STKE, AAAS, Washington, DC 20005, USA
Autophagy provides a mechanism for movement of cytoplasmic materials to the lysosomes, where they can be degraded or recycled. Autophagy functions to supply energy during short periods of starvation, but unrestrained autophagy causes cell death. Gohla et al. explored the role of the Gi class of heterotrimeric guanine nucleotide-binding proteins in regulating autophagy. The authors induced autophagy in liver cells in culture by incubating them briefly in culture medium lacking growth factors or amino acids. Gi3 was normally found in the cytosol, but in cells undergoing autophagy, it was redistributed to the plasma membrane and to the endoplasmic reticulum and endosomes. Inhibition of autophagy in cells exposed to insulin or phenylalanine was associated with decreased formation of vesicles and decreased vesicular staining of Gi3. Insulin or phenylalanine also reversed autophagy in mouse livers perfused with buffer lacking amino acids in vivo, and these effects were inhibited by pertussis toxin, an inhibitor of Gi function. However, neither insulin nor amino acids are thought to directly activate Gi signaling. Nevertheless, the antiautophagic action of insulin was almost completely absent in perfused livers from knockout mice lacking Gi3. The authors note that the findings strongly implicate Gi3 in regulation of autophagy and raise intriguing questions about the nature of the upstream signals that may control Gi3 activity in response to nutrients and growth factors, given that G protein-coupled receptors are normally not found on intracellular membranes.
A. Gohla, K. Klement, R. P. Piekorz, K. Pexa, S. vom Dahl, K. Spicher, V. Dreval, D. Häussinger, L. Birnbaumer, B. Nürnberg, An obligatory requirement for the heterotrimeric G protein Gi3 in the antiautophagic action of insulin in the liver. Proc. Natl. Acad. Sci. U.S.A. 104, 3003-3008 (2007). [Abstract] [Full Text]
Citation: L. B. Ray, G Protein-Mediated Inhibition of Autophagy. Sci. STKE 2007, tw66 (2007).
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