Invited Review the Cytoskeleton in Skeletal, Cardiac and Smooth
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0270.6474/84/0408-1933$02.00/O The Journal of Neuroscience Copyright 0 Society for Neuroscience Vol. 4, No. 8, pp. 1933-1943 Printed in U.S.A. August 1984 PARTIAL PURIFICATION AND FUNCTIONAL IDENTIFICATION OF A CALMODULIN-ACTIVATED, ADENOSINE 5’-TRIPHOSPHATE-DEPENDENT CALCIUM PUMP FROM SYNAPTIC PLASMA MEMBRANES1 DIANE M. PAPAZIAN,* HANNAH RAHAMIMOFF,$ AND STANLEY M. GOLDIN§’ Departments of *Biological Chemistry and $Pharmacology, Harvard Medical School, Boston, Massachusetts 02115 and *Department of Biochemistry, Hadassah Medical School, Hebrew University, Jerusalem, Israel Received July 18, 1983; Revised February 27, 1984; Accepted February 28, 1984 Abstract Synaptic plasma membranes isolated from rat brain contain a calmodulin-activated Ca2+ pump. It has been purified 80- to 160-fold by solubilization with Triton X-100 and affinity chromatography on a calmodulin- Sepharose 4B column. After reconstitution into phospholipid vesicles, the affinity-purified pump efficiently catalyzed ATP dependent Ca2+ transport, which was activated 7- to g-fold by calmodulin. The major protein component of the affinity-purified preparation had a M, = 140,000; it was virtually the only band visualized on a Coomassie blue-stained SDS polyacrylamide gel. It has been identified as the Ca”’ pump by two functional criteria. First, it was phosphorylated by [y-““P]ATP in a Ca’+-dependent manner; the phosphorylated protein had the chemical reactivity of an acyl phosphate, characteristic of the phosphorylated intermediates of ion-transporting ATPases. Second, the protein was enriched by transport-specific fractiona- tion, a density gradient procedure which uses the transport properties of the reconstituted Ca2+ pump as a physical tool for its purification. -
Microanatomy of Muscles
Microanatomy of Muscles Anatomy & Physiology Class Three Main Muscle Types Objectives: By the end of this presentation you will have the information to: 1. Describe the 3 main types of muscles. 2. Detail the functions of the muscle system. 3. Correctly label the parts of a myocyte (muscle cell) 4. Identify the levels of organization in a skeletal muscle from organ to myosin. 5. Explain how a muscle contracts utilizing the correct terminology of the sliding filament theory. 6. Contrast and compare cardiac and smooth muscle with skeletal muscle. Major Functions: Muscle System 1. Moving the skeletal system and posture. 2. Passing food through the digestive system & constriction of other internal organs. 3. Production of body heat. 4. Pumping the blood throughout the body. 5. Communication - writing and verbal Specialized Cells (Myocytes) ~ Contractile Cells Can shorten along one or more planes because of specialized cell membrane (sarcolemma) and specialized cytoskeleton. Specialized Structures found in Myocytes Sarcolemma: The cell membrane of a muscle cell Transverse tubule: a tubular invagination of the sarcolemma of skeletal or cardiac muscle fibers that surrounds myofibrils; involved in transmitting the action potential from the sarcolemma to the interior of the myofibril. Sarcoplasmic Reticulum: The special type of smooth endoplasmic Myofibrils: reticulum found in smooth and a contractile fibril of skeletal muscle, composed striated muscle fibers whose function mainly of actin and myosin is to store and release calcium ions. Multiple Nuclei (skeletal) & many mitochondria Skeletal Muscle - Microscopic Anatomy A whole skeletal muscle (such as the biceps brachii) is considered an organ of the muscular system. Each organ consists of skeletal muscle tissue, connective tissue, nerve tissue, and blood or vascular tissue. -
VIEW Open Access Muscle Spindle Function in Healthy and Diseased Muscle Stephan Kröger* and Bridgette Watkins
Kröger and Watkins Skeletal Muscle (2021) 11:3 https://doi.org/10.1186/s13395-020-00258-x REVIEW Open Access Muscle spindle function in healthy and diseased muscle Stephan Kröger* and Bridgette Watkins Abstract Almost every muscle contains muscle spindles. These delicate sensory receptors inform the central nervous system (CNS) about changes in the length of individual muscles and the speed of stretching. With this information, the CNS computes the position and movement of our extremities in space, which is a requirement for motor control, for maintaining posture and for a stable gait. Many neuromuscular diseases affect muscle spindle function contributing, among others, to an unstable gait, frequent falls and ataxic behavior in the affected patients. Nevertheless, muscle spindles are usually ignored during examination and analysis of muscle function and when designing therapeutic strategies for neuromuscular diseases. This review summarizes the development and function of muscle spindles and the changes observed under pathological conditions, in particular in the various forms of muscular dystrophies. Keywords: Mechanotransduction, Sensory physiology, Proprioception, Neuromuscular diseases, Intrafusal fibers, Muscular dystrophy In its original sense, the term proprioception refers to development of head control and walking, an early im- sensory information arising in our own musculoskeletal pairment of fine motor skills, sensory ataxia with un- system itself [1–4]. Proprioceptive information informs steady gait, increased stride-to-stride variability in force us about the contractile state and movement of muscles, and step length, an inability to maintain balance with about muscle force, heaviness, stiffness, viscosity and ef- eyes closed (Romberg’s sign), a severely reduced ability fort and, thus, is required for any coordinated move- to identify the direction of joint movements, and an ab- ment, normal gait and for the maintenance of a stable sence of tendon reflexes [6–12]. -
The Role of Z-Disc Proteins in Myopathy and Cardiomyopathy
International Journal of Molecular Sciences Review The Role of Z-disc Proteins in Myopathy and Cardiomyopathy Kirsty Wadmore 1,†, Amar J. Azad 1,† and Katja Gehmlich 1,2,* 1 Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK; [email protected] (K.W.); [email protected] (A.J.A.) 2 Division of Cardiovascular Medicine, Radcliffe Department of Medicine and British Heart Foundation Centre of Research Excellence Oxford, University of Oxford, Oxford OX3 9DU, UK * Correspondence: [email protected]; Tel.: +44-121-414-8259 † These authors contributed equally. Abstract: The Z-disc acts as a protein-rich structure to tether thin filament in the contractile units, the sarcomeres, of striated muscle cells. Proteins found in the Z-disc are integral for maintaining the architecture of the sarcomere. They also enable it to function as a (bio-mechanical) signalling hub. Numerous proteins interact in the Z-disc to facilitate force transduction and intracellular signalling in both cardiac and skeletal muscle. This review will focus on six key Z-disc proteins: α-actinin 2, filamin C, myopalladin, myotilin, telethonin and Z-disc alternatively spliced PDZ-motif (ZASP), which have all been linked to myopathies and cardiomyopathies. We will summarise pathogenic variants identified in the six genes coding for these proteins and look at their involvement in myopathy and cardiomyopathy. Listing the Minor Allele Frequency (MAF) of these variants in the Genome Aggregation Database (GnomAD) version 3.1 will help to critically re-evaluate pathogenicity based on variant frequency in normal population cohorts. -
Genetic Mutations and Mechanisms in Dilated Cardiomyopathy
Genetic mutations and mechanisms in dilated cardiomyopathy Elizabeth M. McNally, … , Jessica R. Golbus, Megan J. Puckelwartz J Clin Invest. 2013;123(1):19-26. https://doi.org/10.1172/JCI62862. Review Series Genetic mutations account for a significant percentage of cardiomyopathies, which are a leading cause of congestive heart failure. In hypertrophic cardiomyopathy (HCM), cardiac output is limited by the thickened myocardium through impaired filling and outflow. Mutations in the genes encoding the thick filament components myosin heavy chain and myosin binding protein C (MYH7 and MYBPC3) together explain 75% of inherited HCMs, leading to the observation that HCM is a disease of the sarcomere. Many mutations are “private” or rare variants, often unique to families. In contrast, dilated cardiomyopathy (DCM) is far more genetically heterogeneous, with mutations in genes encoding cytoskeletal, nucleoskeletal, mitochondrial, and calcium-handling proteins. DCM is characterized by enlarged ventricular dimensions and impaired systolic and diastolic function. Private mutations account for most DCMs, with few hotspots or recurring mutations. More than 50 single genes are linked to inherited DCM, including many genes that also link to HCM. Relatively few clinical clues guide the diagnosis of inherited DCM, but emerging evidence supports the use of genetic testing to identify those patients at risk for faster disease progression, congestive heart failure, and arrhythmia. Find the latest version: https://jci.me/62862/pdf Review series Genetic mutations and mechanisms in dilated cardiomyopathy Elizabeth M. McNally, Jessica R. Golbus, and Megan J. Puckelwartz Department of Human Genetics, University of Chicago, Chicago, Illinois, USA. Genetic mutations account for a significant percentage of cardiomyopathies, which are a leading cause of conges- tive heart failure. -
Vocabulario De Morfoloxía, Anatomía E Citoloxía Veterinaria
Vocabulario de Morfoloxía, anatomía e citoloxía veterinaria (galego-español-inglés) Servizo de Normalización Lingüística Universidade de Santiago de Compostela COLECCIÓN VOCABULARIOS TEMÁTICOS N.º 4 SERVIZO DE NORMALIZACIÓN LINGÜÍSTICA Vocabulario de Morfoloxía, anatomía e citoloxía veterinaria (galego-español-inglés) 2008 UNIVERSIDADE DE SANTIAGO DE COMPOSTELA VOCABULARIO de morfoloxía, anatomía e citoloxía veterinaria : (galego-español- inglés) / coordinador Xusto A. Rodríguez Río, Servizo de Normalización Lingüística ; autores Matilde Lombardero Fernández ... [et al.]. – Santiago de Compostela : Universidade de Santiago de Compostela, Servizo de Publicacións e Intercambio Científico, 2008. – 369 p. ; 21 cm. – (Vocabularios temáticos ; 4). - D.L. C 2458-2008. – ISBN 978-84-9887-018-3 1.Medicina �������������������������������������������������������������������������veterinaria-Diccionarios�������������������������������������������������. 2.Galego (Lingua)-Glosarios, vocabularios, etc. políglotas. I.Lombardero Fernández, Matilde. II.Rodríguez Rio, Xusto A. coord. III. Universidade de Santiago de Compostela. Servizo de Normalización Lingüística, coord. IV.Universidade de Santiago de Compostela. Servizo de Publicacións e Intercambio Científico, ed. V.Serie. 591.4(038)=699=60=20 Coordinador Xusto A. Rodríguez Río (Área de Terminoloxía. Servizo de Normalización Lingüística. Universidade de Santiago de Compostela) Autoras/res Matilde Lombardero Fernández (doutora en Veterinaria e profesora do Departamento de Anatomía e Produción Animal. -
Influence of Nebulin on the Assembly Mechanics Of
INFLUENCE OF NEBULIN ON THE ASSEMBLY MECHANICS OF DESMIN An Undergraduate Research Scholars Thesis by MARC ADRIAN CARAGEA Submitted to Honors and Undergraduate Research Texas A&M University In partial fulfillment of the requirements for the designation as UNDERGRADUATE RESEARCH SCHOLAR Approved by Research Adviser: Gloria M. Conover, Ph.D. May 2014 Major: Biomedical Sciences TABLE OF CONTENTS Page ABSTRACT ............................................................................................................................... 1 ACKNOWLEDGMENTS ........................................................................................................... 2 NOMENCLATURE .................................................................................................................... 3 CHAPTER I INTRODUCTION ............................................................................................... 4 II MATERIALS AND METHODS ......................................................................... 8 Affinity purification of WT and mutant desmin proteins from bacteria ................ 8 Affinity purification of recombinant Nebulin M160 – 164 ................................... 9 Assembly protocol for desmin precursors into filaments in vitro ...................... 11 Sample preparation for atomic force microscopy ............................................... 11 Single desmin filament length acquisition and analysis ..................................... 13 Determination of Young’s modulus for desmin filament networks ................... -
Muscle Histology
Muscle Histology Dr. Heba Kalbouneh Functions of muscle tissue ▪ Movement ▪ Maintenance of posture ▪ Joint stabilization ▪ Heat generation Types of Muscle Tissue ▪ Skeletal muscle ▪ Cardiac muscle ▪ Smooth muscle Types of Muscle Tissue Skeletal •Attach to and move skeleton •40% of body weight •Fibers = multinucleate cells (embryonic cells fuse) •Cells with obvious striations •Contractions are voluntary Cardiac: only in the wall of the heart •Cells are striated •Contractions are involuntary (not voluntary) Smooth: walls of hollow organs •Lack striations •Contractions are involuntary (not voluntary) Similarities… ▪ Their cells are called fibers because they are elongated ▪ Contraction depends on myofilaments ▪ Actin ▪ Myosin ▪ Plasma membrane is called sarcolemma ▪ Sarcos = flesh ▪ Lemma = sheath SKELETAL MUSCLES Epimysium: surrounds whole muscle Endomysium is around each muscle fiber Perimysium is around fascicle = muscle cell= myofiber Skeletal muscle This big cylinder is a fiber: a cell ▪ Fibers (each is one cell) have striations ▪ Myofibrils are organelles of the cell: these are made -an organelle up of myofilaments ▪ Sarcomere ▪ Basic unit of contraction ▪ Myofibrils are long rows of repeating sarcomeres ▪ Boundaries: Z discs (or lines) Sarcomere M line provides an attachment to myosin filaments Z line provides an attachment to actin filaments A band is the darker band of the myofibril containing myosin filaments H band is the lighter section in the middle of the A band where only myosin is present I band is the lighter band containing -
(7E) Powerpoint Lecture Outline Chapter 8: Control of Movement
Carlson (7e) PowerPoint Lecture Outline Chapter 8: Control of Movement This multimedia product and its contents are protected under copyright law. The following are prohibited by law: •any public performance or display, including transmission of any image over a network; •preparation of any derivative work, including extraction, in whole or in part, of any images; •any rental, lease, or lending of the program. Copyright 2001 by Allyn & Bacon Skeletal Muscle n Movements of our body are accomplished by contraction of the skeletal muscles l Flexion: contraction of a flexor muscle draws in a limb l Extension: contraction of extensor muscle n Skeletal muscle fibers have a striated appearance n Skeletal muscle is composed of two fiber types: l Extrafusal: innervated by alpha-motoneurons from the spinal cord: exert force l Intrafusal: sensory fibers that detect stretch of the muscle u Afferent fibers: report length of intrafusal: when stretched, the fibers stimulate the alpha-neuron that innervates the muscle fiber: maintains muscle tone u Efferent fibers: contraction adjusts sensitivity of afferent fibers. 8.2 Copyright 2001 by Allyn & Bacon Skeletal Muscle Anatomy n Each muscle fiber consists of a bundle of myofibrils l Each myofibril is made up of overlapping strands of actin and myosin l During a muscle twitch, the myosin filaments move relative to the actin filaments, thereby shortening the muscle fiber 8.3 Copyright 2001 by Allyn & Bacon Neuromuscular Junction n The neuromuscular junction is the synapse formed between an alpha motor neuron -
Back-To-Basics: the Intricacies of Muscle Contraction
Back-to- MIOTA Basics: The CONFERENCE OCTOBER 11, Intricacies 2019 CHERI RAMIREZ, MS, of Muscle OTRL Contraction OBJECTIVES: 1.Review the anatomical structure of a skeletal muscle. 2.Review and understand the process and relationship between skeletal muscle contraction with the vital components of the nervous system, endocrine system, and skeletal system. 3.Review the basic similarities and differences between skeletal muscle tissue, smooth muscle tissue, and cardiac muscle tissue. 4.Review the names, locations, origins, and insertions of the skeletal muscles found in the human body. 5.Apply the information learned to enhance clinical practice and understanding of the intricacies and complexity of the skeletal muscle system. 6.Apply the information learned to further educate clients on the importance of skeletal muscle movement, posture, and coordination in the process of rehabilitation, healing, and functional return. 1. Epithelial Four Basic Tissue Categories 2. Muscle 3. Nervous 4. Connective A. Loose Connective B. Bone C. Cartilage D. Blood Introduction There are 3 types of muscle tissue in the muscular system: . Skeletal muscle: Attached to bones of skeleton. Voluntary. Striated. Tubular shape. Cardiac muscle: Makes up most of the wall of the heart. Involuntary. Striated with intercalated discs. Branched shape. Smooth muscle: Found in walls of internal organs and walls of vascular system. Involuntary. Non-striated. Spindle shape. 4 Structure of a Skeletal Muscle Skeletal Muscles: Skeletal muscles are composed of: • Skeletal muscle tissue • Nervous tissue • Blood • Connective tissues 5 Connective Tissue Coverings Connective tissue coverings over skeletal muscles: .Fascia .Tendons .Aponeuroses 6 Fascia: Definition: Layers of dense connective tissue that separates muscle from adjacent muscles, by surrounding each muscle belly. -
Troponin Variants in Congenital Myopathies: How They Affect Skeletal Muscle Mechanics
International Journal of Molecular Sciences Review Troponin Variants in Congenital Myopathies: How They Affect Skeletal Muscle Mechanics Martijn van de Locht , Tamara C. Borsboom, Josine M. Winter and Coen A. C. Ottenheijm * Department of Physiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Location VUmc, 1081 HZ Amsterdam, The Netherlands; [email protected] (M.v.d.L.); [email protected] (T.C.B.); [email protected] (J.M.W.) * Correspondence: [email protected]; Tel.: +31-(0)-20-444-8123 Abstract: The troponin complex is a key regulator of muscle contraction. Multiple variants in skeletal troponin encoding genes result in congenital myopathies. TNNC2 has been implicated in a novel congenital myopathy, TNNI2 and TNNT3 in distal arthrogryposis (DA), and TNNT1 and TNNT3 in nemaline myopathy (NEM). Variants in skeletal troponin encoding genes compromise sarcomere function, e.g., by altering the Ca2+ sensitivity of force or by inducing atrophy. Several potential therapeutic strategies are available to counter the effects of variants, such as troponin activators, introduction of wild-type protein through AAV gene therapy, and myosin modulation to improve muscle contraction. The mechanisms underlying the pathophysiological effects of the variants in skeletal troponin encoding genes are incompletely understood. Furthermore, limited knowledge is available on the structure of skeletal troponin. This review focusses on the physiology of slow and fast skeletal troponin and the pathophysiology of reported variants in skeletal troponin encoding genes. A better understanding of the pathophysiological effects of these variants, together with enhanced knowledge regarding the structure of slow and fast skeletal troponin, will direct the development of Citation: van de Locht, M.; treatment strategies. -
CAP2 Deficiency Delays Myofibril Actin Cytoskeleton Differentiation and Disturbs Skeletal Muscle Architecture and Function
CAP2 deficiency delays myofibril actin cytoskeleton differentiation and disturbs skeletal muscle architecture and function Lara-Jane Kepsera, Fidan Damara, Teresa De Ciccob, Christine Chaponnierc, Tomasz J. Prószynski b, Axel Pagenstecherd, and Marco B. Rusta,e,f,1 aMolecular Neurobiology Group, Institute of Physiological Chemistry, University of Marburg, 35032 Marburg, Germany; bLaboratory of Synaptogenesis, Nencki Institute of Experimental Biology PAS, 02-093 Warsaw, Poland; cDepartment of Pathology and Immunology, University of Geneva, 1211 Geneva, Switzerland; dInstitute of Neuropathology, University of Marburg, 35032 Marburg, Germany; eCenter for Mind, Brain and Behavior, Research Campus of Central Hessen, 35032 Marburg, Germany; and fDFG Research Training Group “Membrane Plasticity in Tissue Development and Remodeling,” GRK 2213, University of Marburg, 35032 Marburg, Germany Edited by Yale E. Goldman, University of Pennsylvania/PMI, Philadelphia, PA, and approved March 14, 2019 (received for review August 7, 2018) Actin filaments (F-actin) are key components of sarcomeres, the have acquired specific functions. While previous analyses of mu- basic contractile units of skeletal muscle myofibrils. A crucial step tant mice demonstrated a role of CAP2 in neuron morphology and during myofibril differentiation is the sequential exchange of heart physiology (13–15), its function in skeletal muscles has not α-actin isoforms from smooth muscle (α-SMA) and cardiac (α-CAA) been investigated, yet. to skeletal muscle α-actin (α-SKA) that, in mice, occurs during early We here report a function for CAP2 in skeletal muscle de- postnatal life. This “α-actin switch” requires the coordinated activ- velopment. We found that CAP2 controls the exchange of ity of actin regulators because it is vital that sarcomere structure α-actin isoforms during myofibril differentiation.