Phosphorylation of α-syntrophin is responsible for its subcellular localization and interaction with dystrophin in muscle cells

79-85Syntrophin is a well-known adaptor protein that links intracellular proteins with the dystrophin-glycoprotein complex (DGC) at the sarcolemma. However, little is known about the underlying mechanism that regulates the intracellular localization of α-syntrophin and its interaction with dystrophin. In this study, we demonstrate that α-syntrophin phosphorylation determines its intracellular localization and interaction with dystrophin in muscle cells. α-Syntrophin, a predominant isoform in skeletal muscles, directly interacts with ion channels, enzymes, receptors, and DGC proteins. Despite α-syntrophin being a potential signaling molecule, most studies focus on its function as a dystrophin-associated protein. However, we previously reported that α-syntrophin has a variety of DGC-independent functions to modulate cell migration, differentiation, survival, and protein stability. According to the results of the in vitro phosphorylation assays using subcellular fractions, the phosphorylated α-syntrophin accumulated only at the plasma membrane, and this event occurred regardless of dystrophin expression. However, the α-syntrophin interacting with dystrophin at the membrane was not in a phosphorylated state. We also identified that protein kinase C (PKC) was involved in the phosphorylation of α-syntrophin, which restricted α-syntrophin to interact with dystrophin. In conclusion, we demonstrate that the phosphorylation of α-syntrophin by PKC regulates its intracellular localization and interaction with dystrophin

Phosphorylation of α-syntrophin is responsible for its subcellular localization and interaction with dystrophin in muscle cells

Syntrophin is a well-known adaptor protein that links intracellular proteins with the dystrophin-glycoprotein complex (DGC) at the sarcolemma. However, little is known about the underlying mechanism that regulates the intracellular localization of α-syntrophin and its interaction with dystrophin. In this study, we demonstrate that α-syntrophin phosphorylation determines its intracellular localization and interaction with dystrophin in muscle cells. α-Syntrophin, a predominant isoform in skeletal muscles, directly interacts with ion channels, enzymes, receptors, and DGC proteins. Despite α-syntrophin being a potential signaling molecule, most studies focus on its function as a dystrophin-associated protein. However, we previously reported that α-syntrophin has a variety of DGC-independent functions to modulate cell migration, differentiation, survival, and protein stability. According to the results of the in vitro phosphorylation assays using subcellular fractions, the phosphorylated α-syntrophin accumulated only at the plasma membrane, and this event occurred regardless of dystrophin expression. However, the α-syntrophin interacting with dystrophin at the membrane was not in a phosphorylated state. We also identified that protein kinase C (PKC) was involved in the phosphorylation of α-syntrophin, which restricted α-syntrophin to interact with dystrophin. In conclusion, we demonstrate that the phosphorylation of α-syntrophin by PKC regulates its intracellular localization and interaction with dystrophin

Structure-activity relationships of fluorene compounds inhibiting HCV variants

Approximately 71 million people suffer from hepatitis C virus (HCV) infection worldwide. Persistent HCV infection causes liver diseases such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma, resulting in approximately 400,000 deaths annually. Effective direct-acting antiviral agents (DAAs) have been developed and are currently used for HCV treatment targeting the following three proteins: NS3/4A proteinase that cleaves the HCV polyprotein into various functional proteins, RNA-dependent RNA polymerase (designated as NS5B), and NS5A, which is required for the formation of double membrane vesicles serving as RNA replication organelles. At least one compound inhibiting NS5A is included in current HCV treatment regimens due to the high efficacy and low toxicity of drugs targeting NS5A. Here we report fluorene compounds showing strong inhibitory effects on GT 1b and 3a of HCV. Moreover, some compounds were effective against resistance-associated variants to DAAs. The structure-activity relationships of the compounds were analyzed. Furthermore, we investigated the molecular bases of the inhibitory activities of some compounds by the molecular docking method.11Ysciescopu

Actin Cytoskeleton and Golgi Involvement in Barley stripe mosaic virus Movement and Cell Wall Localization of Triple Gene Block Proteins.

Barley stripe mosaic virus (BSMV) induces massive actin filament thickening at the infection front of infected Nicotiana benthamiana leaves. To determine the mechanisms leading to actin remodeling, fluorescent protein fusions of the BSMV triple gene block (TGB) proteins were coexpressed in cells with the actin marker DsRed: Talin. TGB ectopic expression experiments revealed that TGB3 is a major elicitor of filament thickening, that TGB2 resulted in formation of intermediate DsRed:Talin filaments, and that TGB1 alone had no obvious effects on actin filament structure. Latrunculin B (LatB) treatments retarded BSMV cell-to-cell movement, disrupted actin filament organization, and dramatically decreased the proportion of paired TGB3 foci appearing at the cell wall (CW). BSMV infection of transgenic plants tagged with GFP-KDEL exhibited membrane proliferation and vesicle formation that were especially evident around the nucleus. Similar membrane proliferation occurred in plants expressing TGB2 and/or TGB3, and DsRed: Talin fluorescence in these plants colocalized with the ER vesicles. TGB3 also associated with the Golgi apparatus and overlapped with cortical vesicles appearing at the cell periphery. Brefeldin A treatments disrupted Golgi and also altered vesicles at the CW, but failed to interfere with TGB CW localization. Our results indicate that actin cytoskeleton interactions are important in BSMV cell-to-cell movement and for CW localization of TGB3

Simple method of measuring ocular rotation in supine position during small incision lenticule extraction

AIM: To introduce a novel measurement method of static cyclotorsion in small incision lenticule extraction (SMILE) and to investigate the effect of preoperative parameters on cyclotorsion and the effect of cyclotorsion on postoperative outcomes. METHODS: The medical records of 242 patients and 484 eyes who underwent SMILE surgery were retrospectively reviewed. Preoperative intraocular pressure, refractive error, and corneal thickness were investigated. Refractive values and visual acuity were measured at 1d, 1, 3, and 6mo. Ocular cyclotorsion in the supine position was measured by calculating the location and angle of the incision site of the cornea in the anterior slit photograph taken after surgery. RESULTS: Of the total 484 eyes in 242 patients, preoperative mean spherical equivalent (SE) was -4.10±1.64 D, and the mean astigmatism was -0.82±0.74 D. Uncorrected distance visual acuity (UCVA) and SE improved significantly after the surgery. Moreover, 219 (45.2%) eyes had excyclotorsion, 235 (48.6%) eyes had incyclotorsion, and 30 (6.2%) eyes had no torsion. The right eyes tended to be excyclotorted, and the left eyes tended to be incyclotorted (P<0.01). The mean cyclotorsion was 1.18°±3.69°, and the mean absolute value of cyclotorsion was 3.14°±2.26°. The range of cyclotorsion was 0.5°–11.4°. It was found that the smaller the preoperative sphere, the higher the amount of cyclotorsion (r=0.11, P=0.016). There was no significant association between the amount of cyclotorsion and preoperative astigmatism. There was no correlation between sex, preoperative corneal thickness, preoperative intraocular pressure, amount of cyclotorsion, and direction of cyclotorsion. The ratio of right eye excyclotorsion and left eye incyclotorsion on 1d was higher than that at 1, 3, and 6mo (all P<0.01). There was no difference between the 1, 3, and 6mo results in the right and left eyes (P=0.15, P=0.16, respectively). CONCLUSION: The newly devised ocular cyclotorsion measurement method can be used to evaluate ocular cyclotorsion after SMILE. Preoperative SE is associated with the amount of cyclotorsion, however, cyclotorsion doesn't have a significant effect on the results of SMILE surgery

EFFECT OF SPORTS TAPING APPLIED FUNCTIONAL CORRECTION GARMENT FOR ADOLESCENT IDIOPATHIC SCOLIOSIS IMPROVEMENT

The purpose of this research was to analyze the effect of wearing underwear type functional garment for the correction scoliosis by conducting a case study. Two patients wore the garment for 8–week. Cobb’s angle and EMG activities during a gait were measured before and after the treatment for the analysis. Both subjects showed that the activities of the right psoas, biceps femoris and gluteus medius were increased. The Cobb’s angle was decreased after 8-week period of wearing. These results matched with the purpose of developed functional correction wear that induce the right psoas muscle contraction and the left psoas muscle relaxation. It seems to be useful wear for adolescent scoliosis patients who avoid using orthosis, and to use special functional underwear to improve their posture

Two newly recorded species of the genus Herpetogramma (Lepidoptera: Crambidae: Spilomelinae) in Korea

AbstractTwo species of the genus Herpetogramma Lederer are reported for the first time in Korea: Herpetogramma licarsisalis (Walker) and Herpetogramma stultalis (Walker). The description, host plants, adult photographs, and pictures of the male and female genitalia are provided