Rab (Ras-related proteins in brain) GTPases are key proteins responsible for a multiplicity of cellular trafficking processes. Belonging to the family of monomeric GTPases, they are regulated by cycling between their active GTP-bound and inactive GDP-bound conformations. Despite possessing a slow intrinsic GTP hydrolysis activity, Rab proteins rely on RabGAPs (Rab GTPase-activating proteins) that catalyze GTP hydrolysis and consequently inactivate the respective Rab GTPases. Two related RabGAPs, TBC1D1 and TBC1D4 (=AS160) have been described to be associated with obesity-related traits and type 2 diabetes in both mice and humans. Inactivating mutations of TBC1D1 and TBC1D4 lead to substantial changes in trafficking and subcellular distribution of the insulin-responsive glucose transporter GLUT4, and to subsequent alterations in energy substrate metabolism. The activity of the RabGAPs is controlled through complex phosphorylation events mediated by protein kinases including AKT and AMPK, and by putative regulatory interaction partners. However, the dynamics and downstream events following phosphorylation are not well understood. This review focuses on the specific role and regulation of TBC1D1 and TBC1D4 in insulin action.
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June 2018
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The structure of a Nucleosome, in which DNA is wrapped around a histone core. In this issue of Biochemical Society Transactions, Taniguchi et al. review recent advances in exploring Nucleosome-level 3D organization of the genome; for details see pages 491–501.
Review Article|
May 21 2018
Regulation of RabGAPs involved in insulin action
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Celebrating 100 years of insulin research
Samaneh Mafakheri;
Samaneh Mafakheri
1Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz-Center for Diabetes Research at Heinrich Heine University Düsseldorf, Medical Faculty, Düsseldorf, Germany
2German Center for Diabetes Research (DZD), Düsseldorf, Germany
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Alexandra Chadt;
Alexandra Chadt
1Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz-Center for Diabetes Research at Heinrich Heine University Düsseldorf, Medical Faculty, Düsseldorf, Germany
2German Center for Diabetes Research (DZD), Düsseldorf, Germany
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Hadi Al-Hasani
1Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz-Center for Diabetes Research at Heinrich Heine University Düsseldorf, Medical Faculty, Düsseldorf, Germany
2German Center for Diabetes Research (DZD), Düsseldorf, Germany
Correspondence: Hadi Al-Hasani (al-hasani@ddz.uni-duesseldorf.de)
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Publisher: Portland Press Ltd
Received:
December 20 2017
Revision Received:
March 28 2018
Accepted:
April 03 2018
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2018
Biochem Soc Trans (2018) 46 (3): 683–690.
Article history
Received:
December 20 2017
Revision Received:
March 28 2018
Accepted:
April 03 2018
Citation
Samaneh Mafakheri, Alexandra Chadt, Hadi Al-Hasani; Regulation of RabGAPs involved in insulin action. Biochem Soc Trans 19 June 2018; 46 (3): 683–690. doi: https://doi.org/10.1042/BST20170479
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