Deletion of Drosophila muscle LIM protein decreases flight muscle stiffness and power generation. Am J Physiol Cell Physiol 301: C373-C382, 2011. First published May 11, 2011; doi:10.1152/ajpcell.00206.2010 can be found at the Z-disk of sarcomeres where it is hypothesized to be involved in sensing muscle stretch. Loss of murine MLP results in dilated cardiomyopathy, and mutations in human MLP lead to cardiac hypertrophy, indicating a critical role for MLP in maintaining normal cardiac function. Loss of MLP in Drosophila (mlp84B) also leads to muscle dysfunction, providing a model system to examine MLP's mechanism of action. Mlp84B-null flies that survive to adulthood are not able to fly or beat their wings. Transgenic expression of the mlp84B gene in the Mlp84B-null background rescues flight ability and restores wing beating ability. Mechanical analysis of skinned flight muscle fibers showed a 30% decrease in oscillatory power production and a slight increase in the frequency at which maximum power is generated for fibers lacking Mlp84B compared with rescued fibers. Mlp84B-null muscle fibers displayed a 25% decrease in passive, active, and rigor stiffness compared with rescued fibers, but no significant decrease in isometric tension generation was observed. Muscle ultrastructure of Mlp84B-null muscle fibers is grossly normal; however, the null fibers have a slight decrease, 11%, in thick filament number per unit cross-sectional area. Our data indicate that MLP contributes to muscle stiffness and is necessary for maximum work and power generation. muscle mechanics; wing beat frequency STRIATED MUSCLE IS A HIGHLY organized tissue that relies on regulated protein-protein interactions to perform its contractile functions. While actin-myosin interactions between the thick and thin filaments generate contractile force, the Z-disk serves as a conduit for this force to be transmitted through neighboring sarcomeres to muscle insertion points or tendons, and to the muscle cell membrane. Therefore, proper assembly, maintenance, and stiffness of the Z-disk are critical for efficient force transmission and power output by striated muscle. Proteins that cross-link actin at the Z-disk are a major contributor to Z-disk stiffness (28). While the major actin cross-linking protein in the Z-disk is ␣-actinin, genetic and biochemical studies indicate that other Z-disk-associated proteins also have important roles in maintaining Z-disk structure and function (17,50,55).Muscle LIM protein (MLP) is a LIM domain protein found at the Z-disk that associates with several other Z-disk proteins including ␣-actinin (27) and Titin via Tcap/telethonin (22). Mice lacking MLP develop dilated cardiomyopathy (3), and mutations in human MLP are linked to familial hypertrophic cardiomyopathy (2,5,13,22,35,38,49), indicating its importance for maintaining normal cardiac function. Characterization of the MLP-null mice indicate that while striated muscle development proceeds normally, the MLP-deficient hearts exhibit several defects including a widening...
A 21-month-old girl with asthma and eczema (treated by albuterol and topical hydrocortisone as needed) presents in January with 5 days of cough, rhinorrhea, and fever. One day before presentation, she developed emesis and diarrhea with a decrease in oral intake and urine output.On presentation, her temperature is 101.7ºF (38.7ºC), with a respiratory rate of 60 breaths per minute, a pulse of 160 beats per minute, blood pressure of 110/68 mm Hg, and an oxygen saturation of 91% on room air. Mucous membranes are dry, and capillary refill is delayed. She is responsive but in moderate respiratory distress with intercostal and subcostal retractions. Crackles and coarse breath sounds are auscultated bilaterally. She has abdominal distension with significant right upper quadrant tenderness and guarding.Laboratory results are remarkable for a blood glucose level of 40 mg/dL (2.2 mmol/L), venous pH 7.15, lactate level of 73.9 mg/dL (8.2 mmol/L), bicarbonate level of 16 mEq/L (16 mmol/L) with an anion gap of 17 mEq/L (17 mmol/L), aspartate aminotransaminase (AST) level of 789 IU/L, and alanine aminotransaminase (ALT) of 301 IU/L. Resuscitation with 25% dextrose achieved normal blood glucose levels, and further fluid resuscitation with 2 normal saline boluses followed by 5% dextrose and 0.45% normal saline was administered. Her total bilirubin level is 1.0 mg/dL (17.1 mmol/L) with an alkaline phosphatase level of 271 IU/L. Serum albumin, protein, amylase, and lipase levels are within normal limits. Abdominal ultrasonography reveals gallbladder wall thickening without evidence of biliary dilatation or cholelithiasis. She subsequently developed coagulopathy with a prothrombin time of 24.4 seconds. Her ammonia level is normal, and urinalysis results are negative for ketones. Acetaminophen, salicylate, urine mass spectrometry, and a 1 -antitrypsin study results are unremarkable. Further evaluation for infectious causes of her symptoms, including a hepatitis panel, viral respiratory polymerase chain reaction panel, cytomegalovirus (CMV), and Epstein-Barr virus titers led to a unifying diagnosis.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.