NSBP-1 mediates the effects of cholesterol on insulin/IGF-1 signaling in Caenorhabditis elegans
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Cellular and Molecular Life Sciences
RESEARCH ARTICLE
NSBP-1 mediates the effects of cholesterol on insulin/IGF-1 signaling in Caenorhabditis elegans Mi Cheong Cheong · Hyoung-Joo Lee · Keun Na · Hyoe-Jin Joo · Leon Avery · Young-Jai You · Young-Ki Paik
Received: 7 August 2012 / Revised: 30 October 2012 / Accepted: 22 November 2012 / Published online: 20 December 2012 © Springer Basel 2012
Abstract Nematode sterol-binding protein 1 (NSBP-1) is a homolog of nucleosome assembly protein 1 in mammals that is expressed widely in Caenorhabditis elegans. NSBP-1 mutants are biologically lethal, demonstrating the significance of the gene in growth and development. We investigated how cholesterol influences the insulin signaling pathway through this novel sterol-binding protein in C. elegans. Here we report that NSBP-1 influences many biological processes mediated by insulin signaling, such as longevity, dauer formation, fat storage, and resistance to oxidative stress. We found that NSBP-1 is phosphorylated by AKT-1 downstream of insulin signaling. In the absence of insulin signaling, NSBP-1 is translocated to the nucleus and binds to DAF-16, a FOXO transcription factor, in a cholesterol-dependent manner. Moreover, NSBP-1 and DAF-16 regulate a common set of genes that can directly modulate
fat storage, longevity, and resistance to stress. Together, our results present a new steroid-binding molecule that can connect sterol signaling to insulin signaling through direct interaction with FOXO. Keywords Cholesterol · Cholesterol-binding protein · C. elegans · D2096.8 · Insulin/IGF-1 signaling · DAF-16 Abbreviations FOXO Forkhead transcription factor HCM High cholesterol medium LCM Low cholesterol medium MLS Mean lifespan NAP Nucleosome assembly protein NSBP Nematode sterol-binding protein
Introduction Electronic supplementary material The online version of this article (doi:10.1007/s00018-012-1221-0) contains supplementary material, which is available to authorized users. M. C. Cheong · H.-J. Lee · K. Na · H.-J. Joo · Y.-K. Paik (*) Department of Biochemistry and Integrated Omics for Biomedical Science (WCU Program), College of Life Science and Biotechnology and Yonsei Proteome Research Center, Yonsei University, 134 Shinchon-dong, Sudaemoon-ku, Seoul 120-749, Korea e-mail: [email protected] Present Address: M. C. Cheong · L. Avery Department of Physiology and Biophysics, Virginia Commonwealth University, Richmond, VA 23298, USA Y.-J. You Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, VA 23298, USA
Cholesterol serves as a plasma membrane component to control membrane fluidity and permeability. It is also a precursor for biologically active molecules, including vitamin D, oxysterols, steroid hormones (such as ecdysone or dafachronic acid), and bile acids. Sterols usually need sterol-binding proteins (SBPs) to regulate sterol homeostasis, trafficking, and cell metabolism. For instance, SREBP and LXR are transcription factors that regulate the expression of genes inv
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