Figure 1 The role of titin in the sarcomere and a summary of isoforms

Slides:



Advertisements
Similar presentations
Week 1 Click images for hyperlinks!. What is a muscle? Muscles are organs made of muscular and connective tissues, which make up the Muscular System They.
Advertisements

MUSCLE TISSUE.
Muscles. Types of Muscle 4 Smooth - involuntary 4 Skeletal - voluntary 4 Cardiac - involuntary.
Lecture 2 Outline: Brief overview of a long history Sarcomere structure and function Myosin Regulation of contraction Paper: A large protein required for.
Motor mechanisms. Keywords (reading p ) Bundle, fiber, myofibril, sarcomere Z-line, thick filament, thin filament Actin, myosin, sliding filament.
18 Sept 07 K Sept 07 Cardiac Contractile Element 1.
OBJECTIVES At the end of this lecture the student should be able to: Define different types of muscles Enumerate cellular organization of human skeletal.
MUSCLE CONTRACTION. Microscopic Anatomy of Skeletal Muscle Sarcomere Contractile unit of a muscle fiber Figure 6.3b.
Transcription Nicky Mulder Acknowledgements: Anna Kramvis for lecture material (adapted here)
II: mechanical engineering
Skeletal Muscle. F11-11 Neuromuscular Junction (nmj): True relay An action potential in the neuron triggers an action potential in the muscle fibre. Thus,
 Produce skeletal movement  By contraction of muscle fibers  True of all = cardiac, smooth, skeletal  Maintain posture/body position  Some muscles.
Regulation of Gene Expression Eukaryotes
Skeletal Muscle: A Specialized Contractile Machine Skeletal Muscle: A Specialized Contractile Machine Lauren C. Pope.
Hair cells, actin bundles, and unconventional myosins.
Motor mechanisms.
Skeletal Muscle Contraction
20 pt 30 pt 40 pt 50 pt 10 pt 20 pt 30 pt 40 pt 50 pt 10 pt 20 pt 30 pt 40 pt 50 pt 10 pt 20 pt 30 pt 40 pt 50 pt 10 pt 20 pt 30 pt 40 pt 50 pt 10 pt Muscle.
3 Types of Muscle Tissue Properties of Muscle Tissue
TCR ( seen here in a ternary complex …) TCR’s come in two flavors…
Physiology of Skeletal Muscle Contraction. The Muscle Action Potential ( AP ) The Muscle Action Potential ( AP ) Muscle RMP = -90 mV ( same as in nerves.
Chapter 49 The Neuromuscular Junction and Muscle Contraction 1.
Muscular System The 3 Types of Muscles SKELETAL MUSCLE STRUCTURE.
Regulation of Gene expression
Muscle contraction Public domain image. Muscle has two purposes Generate motion Generate force.
Date of download: 7/7/2016 Copyright © The American College of Cardiology. All rights reserved. From: Tcap gene mutations in hypertrophic cardiomyopathy.
Epigenetic Control of Gene Expression Readings from Gilbert (10 edition): pp 34-35, (9 th ed 35-36,
Muscles.
Figure 6: BTK splice variants in B cell precursor leukemia
Promoters and expression
Supplementary Materials
John W. Bloom, MD  Journal of Allergy and Clinical Immunology 
Expression of Human Genes
Immunogenetics Lecture 3: TcR.
Robert H. Oakley, PhD, John A. Cidlowski, PhD 
Figure 6 Factors modulating SCN5A gene expression
Eric J. Stöhr, PhD, Hiroo Takayama, MD, PhD, Giovanni Ferrari, PhD 
Volume 97, Issue 8, Pages (October 2009)
A1.
Nat. Rev. Cardiol. doi: /nrcardio
HOPX: The Unusual Homeodomain-Containing Protein
Figure 10 The energy depletion hypothesis
Between Disease-Causing and an Innocent Bystander: The Role of Titin as a Modifier in Hypertrophic Cardiomyopathy  Brenda Gerull, MD  Canadian Journal.
α1-Adrenoceptor Subtype Selectivity and Lower Urinary Tract Symptoms
Muscle Tissue Characteristics of Muscle
CARP: Fishing for Novel Mechanisms of Neovascularization
A Novel Gene Causing a Mendelian Audiogenic Mouse Epilepsy
Cytoskeleton: Titin as a scaffold and spring
Genetic Pathogenesis of Hypertrophic and Dilated Cardiomyopathy
Regulation of Contraction by the Thick Filaments in Skeletal Muscle
Mechanisms and Consequences of Alternative Polyadenylation
RAS Proteins and Their Regulators in Human Disease
Molecular Dissection of N2B Cardiac Titin’s Extensibility
Alternative and aberrant splicing of MDM2 mRNA in human cancer
Two Kinases to Soften the Heart
Figure 2 Ribosome profiling reveals translation of truncating alleles
Volume 5, Issue 6, Pages (November 2012)
Fig. 1. Distribution of TTNtv in healthy individuals and DCM patients, and TTN exon usage in the heart. Distribution of TTNtv in healthy individuals and.
Functional organization and properties of skeletal muscles
Ch. 12 Muscle Three types of muscle Skeletal muscle Anatomy
Nat. Rev. Neurol. doi: /nrneurol
Structure of mdm2 gene and protein
Figure 1 Schematic of the OPA3 gene and OPA3 protein isoform b
MUSCULAR SYSTEM Human Systems.
Volume 7, Issue 1, Pages 1-11 (July 1997)
Hinrich Gronemeyer, Arthur Zelent  Cancer Cell 
Neurodegenerative Tauopathies
S. Lawrence Zipursky, Joshua R. Sanes  Cell 
Splice isoforms of the JNK1, JNK2, and JNK3 proteins.
Update on glucocorticoid action and resistance
Presentation transcript:

Figure 1 The role of titin in the sarcomere and a summary of isoforms Figure 1 | The role of titin in the sarcomere and a summary of isoforms. a | Structure of the sarcomere. The sarcomere is the fundamental contractile unit of striated muscle and comprises interdigitating thick and thin filaments that generate force. Four distinct regions are defined by light microscopy: the Z‑disc, I‑band, A‑band, and M‑line. Individual molecules of titin span the full length of the hemisarcomere, with structural, sensory, and signalling roles. The amino (NH2)-terminus inserts into the Z‑disc, and the carboxyl (COOH)-terminus inserts into the M‑line. The A‑band is closely associated with the thick filament, and the I‑band comprises mainly elastic elements. b | Structure of titin. A diversity of functions is apparent. Titin contains binding sites for other structural proteins; passive force-generating elements, such as the repetitive I‑band immunoglobulin (Ig) domains, PEVK regions, and N2B unique sequences (N2‑bus); and diverse binding sites for other ligands, including a kinase domain. The schematic represents the titin domain structure (UniProt Q8WZ42‑1) and the location of known ligand-binding sites. c | Structure of the TTN gene. TTN contains 364 exons with enormous potential for alternative splicing. An inferred-complete metatranscript comprising 363 exons can be used as a reference for convenience to describe most features. Biologically, two transcripts predominate in the heart — a long and compliant N2BA isoform, and a shorter and stiffer N2B isoform that contains fewer I‑band spring elements. A third isoform, Novex‑3, utilizes an alternative 3′ exon (exon 46) that cannot be represented in the metatranscript and is expressed in the heart at lower levels. Novex‑3 is not thought to span the sarcomere, and its functions are not well characterized. Other low-abundance cardiac transcripts, fetal isoforms, and skeletal muscle isoforms are transcribed from the same gene, but are not shown here. ANKRD, ankyrin repeat domain-containing protein; BIN1, MYC box-dependent-interacting protein 1; BRAF, serine/threonine-protein kinase BRAF; FHL, four and a half LIM domains protein; FN3, fibronectin type III; HSPB1, heat shock protein‑β1; MARP, muscle ankyrin repeat protein; mHSP90, methylated heat shock protein HSP 90; MYBPC, myosin-binding protein C; NBR1, next to BRCA1 gene 1 protein; PKA, cAMP-dependent protein kinase; PKG, cGMP-dependent protein kinase; S100A1, protein S100A1; sANK1, small ankyrin 1 (alternatively spliced variant of ankyrin 1); SMYD2, N‑lysine methyltransferase SMYD2; TRIM55, tripartite motif-containing protein 55; TRIM63, E3 ubiquitin-protein ligase TRIM63. Part b data from REF. 8, and image adapted with permission from REF. 52, John Wiley & Sons. Part b data from Labeit, S. & Kolmerer, B. Titins: giant proteins in charge of muscle ultrastructure and elasticity. Science 270, 293–296 (1995), and image adapted with permission from Chauveau, C., Rowell, J. & Ferreiro, A. A rising titan: TTN review and mutation update. Hum. Mutat. 35, 1046–1059 (2014), John Wiley & Sons Ware, J. S. & Cook, S. A. (2017) Role of titin in cardiomyopathy: from DNA variants to patient stratification Nat. Rev. Cardiol. doi:10.1038/nrcardio.2017.190