SIRT1 Phosphorylation by Casein Kinase 2 in Obesity Inhibits Its Nuclear Localization and Promotes Fatty Liver
SIRT1 prevents and improves many obesity-related diseases, including diabetes and nonalcoholic fatty liver disease (NAFLD). SIRT1 function is aberrantly low in obesity, but the underlying mechanisms are unclear. Choi et al. (e00006-17) show that phosphorylation of SIRT1 at S164 by casein kinase 2 (CK2), hepatic expression of which is dramatically elevated in obesity, inhibits its nuclear localization and deacetylase activity, resulting in defective mitochondrial β-oxidation, liver steatosis, and glucose/insulin intolerance. Remarkably, S164-phosphorylated SIRT1 and CK2 levels are highly elevated in NAFLD patients and correlate with disease severity. SIRT1 phosphorylation may therefore serve as a novel drug target for obesity, diabetes, and NAFLD.
CD9 Regulates Major Histocompatibility Complex Class II Trafficking in Monocyte-Derived Dendritic Cells
Rocha-Perugini et al. (e00202-17) demonstrate that the tetraspanin CD9 is important for antigen presentation by monocyte-derived dendritic cells (MoDCs) through the regulation of major histocompatibility complex class II (MHC-II) trafficking. CD9 deficiency impairs surface MHC-II expression in immature and mature MoDCs, decreasing T-cell-stimulatory capacity. In immature MoDCs, CD9 regulates MHC-II egress from MHC-II-enriched endosomal compartments to the surface and controls the endocytosis of surface MHC-II. In mature MoDCs, MHC-II egress occurs in a CD9-independent manner but CD9 is crucial for the subsequent internalization and recycling of surface MHC-II. Their work underlines the importance of tetraspanin CD9 in the control of MHC-II trafficking and surface expression.
- Copyright © 2017 American Society for Microbiology.
