%0 Journal Article %1 Gohla2007a %A Gohla, A. %A Klement, K. %A Piekorz, R. P. %A Pexa, K. %A vom Dahl, S. %A Spicher, K. %A Dreval, V. %A Haussinger, D. %A Birnbaumer, L. %A Nurnberg, B. %D 2007 %J Proc Natl Acad Sci U S A %K Animals Antibodies/pharmacology Autophagy/*drug Fractions/drug GTP-Binding Gi-Go/immunology/*metabolism Gi2/metabolism Gohla Hepatocytes/cytology/drug Heterotrimeric Insulin/*pharmacology Isoforms/metabolism Liver/*drug Male Mice Post-Translational/drug Processing, Protein Subcellular Subunit, Subunits, Transport/drug alpha effects effects/*metabolism Proteins/metabolism %N 8 %P 3003-8 %T An obligatory requirement for the heterotrimeric G protein Gi3 in the antiautophagic action of insulin in the liver %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17296938 %V 104 %X Heterotrimeric G proteins of the G(i) class have been implicated in signaling pathways regulating growth and metabolism under physiological and pathophysiological conditions. Knockout mice carrying inactivating mutations in both of the widely expressed Galpha(i) class genes, Galpha(i2) and Galpha(i3), demonstrate shared as well as gene-specific functions. The presence of a single active allele of Galpha(i3) is sufficient for embryonic development, whereas at least one allele of Galpha(i2) is required for extrauterine life. Mice lacking both Galpha(i2) and Galpha(i3) are massively growth-retarded and die in utero. We have used biochemical and cell biological methods together with in situ liver perfusion experiments to study Galpha(i) isoform-specific functions in Galpha(i2)- and Galpha(i3)-deficient mice. The subcellular localization of Galpha(i3) in isolated mouse hepatocytes depends on the cellular metabolic status. Galpha(i3) localizes to autophagosomes upon starvation-induced autophagy and distributes to the plasma membrane upon insulin stimulation. Analysis of autophagic proteolysis in perfused mouse livers showed that mice lacking Galpha(i3) are deficient in the inhibitory action of insulin. These data indicate that Galpha(i3) is crucial for the antiautophagic action of insulin and suggest an as-yet-unrecognized function for Galpha(i3) on autophagosomal membranes.

@article{Gohla2007a, abstract = {Heterotrimeric G proteins of the G(i) class have been implicated in signaling pathways regulating growth and metabolism under physiological and pathophysiological conditions. Knockout mice carrying inactivating mutations in both of the widely expressed Galpha(i) class genes, Galpha(i2) and Galpha(i3), demonstrate shared as well as gene-specific functions. The presence of a single active allele of Galpha(i3) is sufficient for embryonic development, whereas at least one allele of Galpha(i2) is required for extrauterine life. Mice lacking both Galpha(i2) and Galpha(i3) are massively growth-retarded and die in utero. We have used biochemical and cell biological methods together with in situ liver perfusion experiments to study Galpha(i) isoform-specific functions in Galpha(i2)- and Galpha(i3)-deficient mice. The subcellular localization of Galpha(i3) in isolated mouse hepatocytes depends on the cellular metabolic status. Galpha(i3) localizes to autophagosomes upon starvation-induced autophagy and distributes to the plasma membrane upon insulin stimulation. Analysis of autophagic proteolysis in perfused mouse livers showed that mice lacking Galpha(i3) are deficient in the inhibitory action of insulin. These data indicate that Galpha(i3) is crucial for the antiautophagic action of insulin and suggest an as-yet-unrecognized function for Galpha(i3) on autophagosomal membranes.}, added-at = {2010-12-14T18:12:02.000+0100}, author = {Gohla, A. and Klement, K. and Piekorz, R. P. and Pexa, K. and vom Dahl, S. and Spicher, K. and Dreval, V. and Haussinger, D. and Birnbaumer, L. and Nurnberg, B.}, biburl = {https://www.bibsonomy.org/bibtex/2537e0f3aadd98699ad6a4b9870aaa638/pharmawuerz}, endnotereftype = {Journal Article}, interhash = {40927d1c855fb85153e973bacdd5a7b2}, intrahash = {537e0f3aadd98699ad6a4b9870aaa638}, issn = {0027-8424 (Print) 0027-8424 (Linking)}, journal = {Proc Natl Acad Sci U S A}, keywords = {Animals Antibodies/pharmacology Autophagy/*drug Fractions/drug GTP-Binding Gi-Go/immunology/*metabolism Gi2/metabolism Gohla Hepatocytes/cytology/drug Heterotrimeric Insulin/*pharmacology Isoforms/metabolism Liver/*drug Male Mice Post-Translational/drug Processing, Protein Subcellular Subunit, Subunits, Transport/drug alpha effects effects/*metabolism Proteins/metabolism}, month = {Feb 20}, note = {Gohla, Antje Klement, Karinna Piekorz, Roland P Pexa, Katja vom Dahl, Stephan Spicher, Karsten Dreval, Vladyslav Haussinger, Dieter Birnbaumer, Lutz Nurnberg, Bernd DK 19318/DK/NIDDK NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States Proceedings of the National Academy of Sciences of the United States of America Proc Natl Acad Sci U S A. 2007 Feb 20;104(8):3003-8. Epub 2007 Feb 12.}, number = 8, pages = {3003-8}, shorttitle = {An obligatory requirement for the heterotrimeric G protein Gi3 in the antiautophagic action of insulin in the liver}, timestamp = {2010-12-14T18:21:42.000+0100}, title = {An obligatory requirement for the heterotrimeric G protein Gi3 in the antiautophagic action of insulin in the liver}, url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17296938}, volume = 104, year = 2007 }