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Updated: May 23, 2026
08:37
Sarcomere Shortening of Pluripotent Stem Cell-Derived Cardiomyocytes using Fluorescent-Tagged Sarcomere Proteins.
Published on: March 3, 2021
The sarcomeric cytoskeleton as a target for pharmacological intervention.
Ay Lin Kho1, Sue Perera, Alexander Alexandrovich
1King's College London BHF Centre of Research Excellence, Randall Division for Cell and Molecular Biophysics and Cardiovascular Division, New Hunt's House, Guy's Campus, London SE1 1UL, United Kingdom.
Current Opinion in Pharmacology
|April 10, 2012
Summary
Sarcomeres, the contractile units in muscles, are emerging as key targets for treating heart and skeletal muscle diseases. Understanding their complex protein network offers new therapeutic strategies.
Area of Science:
- Muscle physiology and molecular biology
- Pharmacological targeting of sarcomeric proteins
Background:
- Heart and skeletal muscle diseases like heart failure and atrophy lack effective treatments.
- Sarcomeres, the contractile units of muscle, are increasingly recognized as potential therapeutic targets.
- The sarcomeric cytoskeleton, composed of giant proteins like titin, obscurin, and nebulin, integrates structural and signaling roles.
Purpose of the Study:
- To review current understanding of sarcomeric cytoskeletal protein signaling in muscle physiology and pathology.
- To explore emerging therapeutic strategies targeting sarcomeric signaling pathways.
- To discuss new aspects of skeletal muscle signaling, pathomechanisms, and treatment.
Main Methods:
- Review of recent scientific literature on sarcomeric protein function and signaling.
- Analysis of physiological and pathological roles of key sarcomeric proteins (titin, obscurin, nebulin).
- Discussion of emerging pharmacological targets and therapeutic approaches.
Main Results:
- Sarcomeric proteins possess signaling domains (e.g., kinase, Rho activator, Src-homology) involved in muscle assembly and adaptation.
- These signaling functions are implicated in both normal muscle function and disease states.
- The potential for targeting these signaling pathways therapeutically is becoming evident.
Conclusions:
- Sarcomeric cytoskeletal proteins are critical for muscle function and adaptation, with emerging roles in disease.
- Targeting the signaling functions of these proteins presents a promising avenue for novel therapies.
- Further research into sarcomeric signaling pathways is crucial for developing effective treatments for muscle diseases.
Related Concept Videos
01:08The Sarcomere
A sarcomere is a microscopic segment repeating in a myofibril. The sarcomere fundamentally consists of two main myofilaments: thick filaments called myosin and thin filaments called actin. These filaments interact by sliding past each other in response to stimulus. In addition to myosin and actin, several other proteins, such as tropomyosin, troponin, titin, nebulin, myomesin, α-actinin, and dystrophin, play crucial roles in regulating, structuring, and functioning of the sarcomere.
Each myosin...
Each myosin...
01:26Cross-bridge Cycle
As muscle contracts, the overlap between the thin and thick filaments increases, decreasing the length of the sarcomere—the contractile unit of the muscle—using energy in the form of ATP. At the molecular level, this is a cyclic, multistep process that involves binding and hydrolysis of ATP, and movement of actin by myosin.
01:10The Role of Actin and Myosin in Non-muscle Cells
Actin and myosin or actomyosin filaments also play a significant role in cells other than those involved in muscle contraction (which occurs within the sarcomere of muscle cells). The mechanism of non-muscle cell contractile bundles was first observed in Dictyostelium and Acanthamoeba. In non-muscle cells, two bundles are commonly found: stress fibers and actomyosin adherence belts. These contractile bundles are smaller and less organized than the ones found in muscle cells. They are held...
01:15Overview of Skeletal Muscle
Skeletal muscles are composed of a bundle of muscle fibers and are attached to bones through tendons. Each skeletal muscle fiber is a single muscle cell. The sarcolemma, the plasma membrane of a skeletal muscle cell, consists of a lipid bilayer and glycocalyx that supports muscle fibers. The sarcolemma extends into the muscle cells to form tubular structures called transverse or T-tubules. Each side of the T-tubules consists of a membrane-bound structure called the sarcoplasmic reticulum,...
01:16Actin and Myosin in Muscle Contraction
Actin and myosin are contractile proteins that form the sarcomere found in skeletal muscle tissues for regulating muscle contraction. Actin, a globular contractile protein, interacts with myosin for muscle contraction. The skeletal tissue appears striped or striated under a microscope due to the repeated arrangement of contractile proteins actin and myosin along the length of myofibrils. Dark A bands and light I bands repeat along myofibrils, and the alignment of myofibrils in the cell causes...
01:13Microscopic Anatomy of Skeletal Muscles
Skeletal muscle cells, also called muscle fibers, are distinctly elongated, multi-nucleated, slender biological units. They are packed with specialized structures designed to facilitate their primary function, which is contraction.
The muscle sarcolemma is a plasma membrane enclosing each muscle cell that conducts electrical signals called action potentials. The sarcolemma extends into the cell to form T-tubules, ensuring the neural impulses are uniformly distributed across the entire muscle...
The muscle sarcolemma is a plasma membrane enclosing each muscle cell that conducts electrical signals called action potentials. The sarcolemma extends into the cell to form T-tubules, ensuring the neural impulses are uniformly distributed across the entire muscle...