Latest Articles
Research ArticleMicroRNA 7 Impairs Insulin Signaling and Regulates Aβ Levels through Posttranscriptional Regulation of the Insulin Receptor Substrate 2, Insulin Receptor, Insulin-Degrading Enzyme, and Liver X Receptor PathwayBrain insulin resistance is a key pathological feature contributing to obesity, diabetes, and neurodegenerative disorders, including Alzheimer’s disease (AD). Besides the classic transcriptional mechanism mediated by hormones, posttranscriptional regulation has recently been shown to regulate a number of signaling pathways that could lead to metabolic diseases.
Research ArticleThe Acetylation of Lysine-376 of G3BP1 Regulates RNA Binding and Stress Granule DynamicsStress granules (SGs) are ribonucleoprotein aggregates that form in response to stress conditions. The regulation of SG dynamics is not fully understood. Permanent pathological SG-like structures were reported in neurodegenerative diseases such as amyotrophic lateral sclerosis. The Ras GTPase-activating protein-binding protein G3BP1 is a central regulator of SG dynamics. We found that the lysine 376 residue (K376) of G3BP1, which is in...
Research Article | SpotlightTIN2 Functions with TPP1/POT1 To Stimulate Telomerase ProcessivityTIN2 is an important regulator of telomere length, and mutations in TINF2, the gene encoding TIN2, cause short-telomere syndromes. While the genetics underscore the importance of TIN2, the mechanism through which TIN2 regulates telomere length remains unclear. Here, we tested the effects of human TIN2 on telomerase activity. We identified a new isoform in human cells, TIN2M, that is expressed at levels similar to those of...
Research ArticlePIKfyve Deficiency in Myeloid Cells Impairs Lysosomal Homeostasis in Macrophages and Promotes Systemic Inflammation in MiceMacrophages are professional phagocytes that are essential for host defense and tissue homeostasis. Proper membrane trafficking and degradative functions of the endolysosomal system are known to be critical for the function of these cells. We have found that PIKfyve, the kinase that synthesizes the endosomal phosphoinositide phosphatidylinositol-3,5-bisphosphate, is an essential regulator of lysosomal biogenesis and degradative...
Research Article1-Palmitoyl-2-Linoleoyl-3-Acetyl-rac-Glycerol Attenuates Streptozotocin-Induced Pancreatic Beta Cell Damage by Promoting Glucose Transporter 2 EndocytosisStreptozotocin (STZ) is widely used to induce diabetic rodent models. It is specifically toxic to pancreatic beta cells and causes severe destruction and dysfunction. We investigated the effect of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) on an STZ-induced diabetic mouse model. PLAG attenuated the glucose increase and maintained serum insulin at levels similar to those seen with control mice.
Research ArticleCorrection of Glycogen Synthase Kinase 3β in Myotonic Dystrophy 1 Reduces the Mutant RNA and Improves Postnatal Survival of DMSXL MiceMyotonic dystrophy type 1 (DM1) is a multisystem neuromuscular disease without cure. One of the possible therapeutic approaches for DM1 is correction of the RNA-binding proteins CUGBP1 and MBNL1, misregulated in DM1. CUGBP1 activity is controlled by glycogen synthase kinase 3β (GSK3β), which is elevated in skeletal muscle of patients with DM1, and inhibitors of GSK3 were suggested as therapeutic molecules to correct CUGBP1 activity in...
Research ArticleDirect and Specific Functional Evaluation of the Nrf2 and MafG Heterodimer by Introducing a Tethered Dimer into Small Maf-Deficient Cells...A group of cytoprotective genes is regulated by heterodimers composed of the cap’n’collar (CNC) family member Nrf2 and one of the small Maf (sMaf) proteins (MafF, MafG, or MafK) through the antioxidant response element (ARE, also referred to as the CNC-sMaf binding element [CsMBE]). Many lines of evidence support this model; however, a direct and specific evaluation of the Nrf2-sMaf heterodimer remains to be executed.
Research Article | SpotlightDuring Adipocyte Remodeling, Lipid Droplet Configurations Regulate Insulin Sensitivity through F-Actin and G-Actin ReorganizationAdipocytes have unique morphological traits in insulin sensitivity control. However, how the appearance of adipocytes can determine insulin sensitivity has not been understood. Here, we demonstrate that actin cytoskeleton reorganization upon lipid droplet (LD) configurations in adipocytes plays important roles in insulin-dependent glucose uptake by regulating GLUT4 trafficking.
