A5036709935- Cardiomyopathy and Myosin Studies
- Muscle Physiology and Disorders
- Cardiovascular Effects of Exercise
- Force Microscopy Techniques and Applications
- Molecular Junctions and Nanostructures
- Ubiquitin and proteasome pathways
- Microtubule and mitosis dynamics
- Cellular transport and secretion
- Nuclear Structure and Function
- Cellular Mechanics and Interactions
- Histone Deacetylase Inhibitors Research
- Cardiovascular Function and Risk Factors
- Acute Myeloid Leukemia Research
- Nutrition and Health in Aging
- RNA Research and Splicing
- Autophagy in Disease and Therapy
- Genetic Neurodegenerative Diseases
- Genetics and Neurodevelopmental Disorders
- Chromosomal and Genetic Variations
- Genetics, Bioinformatics, and Biomedical Research
- Inflammasome and immune disorders
- Fuel Cells and Related Materials
- Machine Learning in Materials Science
- Endoplasmic Reticulum Stress and Disease
- Phagocytosis and Immune Regulation
Medizinische Hochschule Hannover
2009-2024
MRC Laboratory of Molecular Biology
2012
Abstract Excessive activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome is involved in many chronic inflammatory diseases, including cardiovascular and Alzheimer’s disease. Here we show that microtubule-affinity regulating kinase 4 (MARK4) binds to NLRP3 drives it microtubule-organizing centre, enabling formation one large speck complex within a single cell. MARK4 knockdown or knockout, disruption MARK4-NLRP3 interaction, impairs spatial arrangement limits activation....
Myosin II is the main force-generating motor during muscle contraction. exists as different isoforms that are involved in diverse physiological functions. One outstanding question whether myosin heavy chain (MHC) alone account for these distinct properties. Unique sets of essential and regulatory light chains (RLCs) known to assemble with specific MHCs, raising intriguing possibility contribute specialized Here, we asked RLCs this functional diversification. To end, generated chimeric motors...
Abstract Background Chemotherapy is the first line of treatment for cancer patients. However, side effects cause severe muscle atrophy or chemotherapy‐induced cachexia. Previously, NF‐κB/MuRF1‐dependent pathway was shown to induce We hypothesized that acute collateral toxic chemotherapy on muscles might involve other unknown pathways promoting atrophy. In this study, we investigated differential chemotherapeutic drugs and probed whether alternative molecular mechanisms lead Methods employed...
Precise assembly of the sarcomere, a force-generating unit in striated muscles, is critical for muscle contraction. Defective sarcomere organization linked to myopathies and cachexia. The molecular mechanisms concerning are poorly understood. Here, we report that SUMO-specific isopeptidase SENP3 determines by specifically regulating sarcomeric contractile myosin heavy-chain gene MyHC-II. ability mature cells severely compromised SENP3-depleted cells. Mechanistically, associated with SETD7...
Coupling of ATP hydrolysis to structural changes in the motor domain is fundamental driving motile functions by myosins. Current understanding this chemomechanical coupling primarily based on ensemble average measurements solution and muscle fibers. Although important, averaging could potentially mask essential details coupling, particularly for mixed populations molecules. Here, we demonstrate potential studying individual myosin molecules, one one, unique insights into established systems...
Abstract Myosin family motors play diverse cellular roles. Precise insights into how the light chains contribute to functional variabilities among myosin motors, however, remain unresolved. Here, it is demonstrated that fast skeletal muscle II isoform heavy chain (MHC‐IID) can be transformed a processive motor, by simply replacing native regulatory MLC2f with variant MLC2v from slow II. Single molecule kinetic analyses and optical trapping measurements of hybrid motor reveal marked changes...
The myosin II motors are ATP-powered force-generating machines driving cardiac and muscle contraction. Myosin heavy chain isoform-beta (β-MyHC) is primarily expressed in the ventricular myocardium slow-twitch fibers, such as M. soleus. soleus-derived (SolM-II) often used an alternative to β-cardiac (βM-II); however, direct assessment of biochemical mechanical features native myosins limited. By employing optical trapping, we examined mechanochemical properties isolated from rabbit heart...
A long life with controlled movement: Engineered protein nanomachines defined and adjustable functional features offer opportunities for controlling movement on nano- to microscale biohybrid devices. Myosin motors (the picture shows a dimeric motor) have now been constructed optimized properties regard stability regulation, including switchable processivity tight control of the velocity movement. Detailed facts importance specialist readers are published as "Supporting Information". Such...
Abstract Background Metal ions play vital roles in regulating various biological systems, making it essential to control the concentration of free metal solutions during experimental procedures. Several software applications exist for estimating metals presence chelators, with MaxChelator being easily accessible choice this domain. This work aimed at developing a Python version arbitrary precision calculations, extensive new features, and user-friendly interface calculate ions. Results We...
The β-myosin heavy chain expressed in ventricular myocardium and the myosin (MyHC) slow-twitch skeletal Musculus soleus (M. soleus) type-I fibers are both encoded by MYH7. Thus, these molecules deemed equivalent. However, some reports suggested variations light composition between M. myosin, which could influence functional parameters, such as maximum velocity of shortening. To test for differences actin gliding on immobilized molecules, we made use vitro motility assays. We found that moved...
How various myosin isoforms fulfill the diverse physiological requirements of distinct muscle types remain unclear. Myosin II expressed in skeletal muscles determine mechanical performance specific muscles. Here, we employed a single-molecule optical trapping method and compared chemomechanical properties slow fast isoforms. Stiffness motor is key to its force-generating ability during contraction. We found that acto-myosin (AM) cross-bridge stiffness depends on nucleotide state as...
Summary Adverse effects of chemotherapies can outweigh the benefits in cancer patients. Various chemotherapeutics are linked to muscle wasting or cachexia, drastically reducing chance survivability Insights into molecular basis chemotherapy-induced cachexia is an unmet need improve treatment strategies. Here, we investigated tyrosine kinase inhibitor class chemotherapeutic agents for their on function. Sorafenib, but not Nilotinib and Imatinib, triggered cachexia. System-wide transcriptome...
Abstract Myosins are ATP‐powered, force‐generating motor proteins involved in cardiac and muscle contraction. The external load experienced by the myosins modulates coordinates their function vivo. Here, this study investigates tension‐sensing mechanisms of rabbit native β‐cardiac myosin (βM‐II) slow skeletal (SolM‐II) that perform different physiological settings. Using mobile optical tweezers with a square wave‐scanning mode, range assisting resisting loads from 0 to 15 pN is exerted on...
Abstract Myosin II is the main force generating motor during muscle contraction. exists as different isoforms, involved in diverse physiological functions. The outstanding question whether myosin heavy chain (MHC) isoforms alone account for distinct properties. Unique sets of essential and regulatory light chains (RLCs) assembled with specific MHCs raises an interesting possibility specialization functions via (LCs). Here, we ask RLCs contribute to functional diversification. To investigate...
Abstract The β-myosin heavy chain expressed in ventricular myocardium and the myosin (MyHC) slow-twitch skeletal soleus muscle type-I fibers are both encoded by MYH7 . Thus, these molecules deemed equivalent. However, some reports suggested variations light composition between myosin, which could influence functional parameters such as maximum velocity of shortening. To test for differences actin gliding on immobilized we made use vitro motility assay. We found that moved filaments with...
Langes Leben mit kontrollierter Bewegung: Maßgeschneiderte Proteinnanomaschinen eindeutigen und anpassbaren Funktionen ermöglichen eine Kontrolle der Bewegung auf nano- bis mikroskaligen Biohybrid-Funktionseinheiten. Myosinmotoren (im Bild ist ein dimerer gezeigt) optimierten Eigenschaften hinsichtlich Stabilität Steuerung, einschließlich schaltbarer Prozessivität Feinsteuerung Geschwindigkeit Bewegung, wurden nun entwickelt.