Retta - L7

Myosin and Muscle Contraction

• Myosin is a major motor protein essential for muscle contraction, particularly myosin-II.
• Myosin-II forms a dimer consisting of two identical heavy chains with a globular ATPase head and a long coiled-coil tail.
• The head domain of myosin can hydrolyze ATP, enabling conformational changes necessary for its motor function.
• Myosin filaments, or thick filaments, consist of many myosin-II dimers arranged antiparallel, projecting heads that interact with actin.

Mechanism of Muscle Contraction

• The contraction cycle begins when ATP binds to the myosin head, inducing its release from actin.
• ATP is then hydrolyzed, which repositions the myosin head towards the plus end of the actin filament.
• The release of inorganic phosphate promotes a strong interaction between myosin and actin, triggering the power stroke where myosin pulls the actin filament.
• The continuous cycling of ATP binding and hydrolysis facilitates sliding of actin filaments relative to myosin, resulting in muscle contraction.

Non-Muscle Functions of Myosin

• Myosin-II isoforms also function in non-muscle cells, participating in cellular contractility and movement.
• In non-muscle cells, myosin-II is not organized into sarcomeres but forms small bipolar filaments regulated by phosphorylation from myosin light-chain kinase (MLCK).
• MLCK is activated by signaling pathways, influencing myosin activity and enabling contractile properties in non-muscle cells.

Diverse Myosin Isoforms

• Myosin-I operates as a monomer, facilitating movement near the cell membrane and supporting cellular processes like vesicle trafficking.
• Myosin-V transports organelles, such as mitochondria, along actin filaments, functioning as a cargo carrier with specific cargo recognition.
• Myosin-V consists of two head domains that allow it to move towards the plus end of actin for organelle distribution.
• Myosin-VI is unique, moving toward the minus end of actin filaments due to a distinct insertion in its head domain.

Key Attributes of Skeletal Muscle Cells

• Skeletal muscle fibers, or cells, are multinucleated structures resulting from the fusion of precursor cells (myoblasts).
• Muscle fibers typically have a diameter of 50 μm and can be several centimeters long.
• Myofibrils within muscle fibers, the contractile units, are cylindrical and aligned in parallel, playing a critical role in muscle contraction.

Visualization and Experimental Approaches

• Techniques like electron microscopy and atomic force microscopy are utilized to observe myosin and actin interactions during movement.
• Fluorescent labeling allows visualization of actin and myosin dynamics in vitro, aiding understanding of muscle contraction mechanisms.
• The study of these motor proteins identifies potential therapeutic targets for muscular disorders and provides insights into cell physiology.### Sarcomeres in Skeletal Muscle
• Sarcomeres are the basic contractile units of myofibrils, approximately 2.2 μm long, contributing to the striated muscle appearance.
• Each sarcomere consists of two Z discs, a dark band (formed by superimposed thick and thin filaments), and a light band at the periphery.
• Thick filaments (myosin) are in the middle, while thin filaments (actin) are attached to the Z discs on both sides.
• Contraction occurs as the myosin heads interact with actin, causing actin filaments to slide toward the center of the sarcomere, effectively reducing the Z disc distance.

Sliding Filament Model

• Thick filaments are surrounded by thin filaments in a hexagonal arrangement, crucial for muscle contraction.
• Myosin head domains bind transiently to actin filaments, allowing for multiple simultaneous interactions that facilitate contraction.
• The process relies on brief interactions, differing from vesicular transport, where motor proteins remain attached for longer durations.

Capping Proteins

• Proteins such as CapZ and tropomodulin cap the ends of actin filaments, preventing their elongation and maintaining stability.
• Alpha actinin is present at the Z disc, maintaining proper spacing between actin filaments.
• Titin anchors thick filaments to Z discs, functioning like a spring during muscle relaxation.
• Nebulin acts as a molecular ruler, ensuring proper length of actin filaments.

Accessory Proteins

• Accessory proteins are crucial for maintaining the structure and function of the sarcomere.
• Alpha actinin contributes to the distance between actin filaments at the Z disc, while capping proteins regulate filament dynamics.
• The assembly of actin filaments is aided by proteins such as formin, ensuring proper structure formation during muscle development.

Signaling Events in Muscle Contraction

• Tropomyosin stabilizes actin filaments and blocks myosin binding sites when muscles are relaxed.
• Upon stimulation, calcium ions released from the sarcoplasmic reticulum bind to troponin C, inducing conformational changes that expose actin binding sites.
• Troponin I inhibits myosin binding when calcium is absent, while calcium binding removes this inhibition.

Calcium Ion Release

• T tubules, invaginations of the plasma membrane, are in contact with the sarcoplasmic reticulum (SR) and contain voltage-gated calcium channels.
• Action potential from nerve cells causes depolarization, opening calcium channels in both T tubules and the SR, releasing calcium into the cytosol.
• Muscle relaxation requires the removal of calcium ions from the cytosol back to the sarcoplasmic reticulum via calcium pumps, which consume ATP.

Energy Requirements for Muscle Contraction

• Muscle contraction and relaxation require significant energy, primarily for myosin head movement and calcium pumping back into the SR.
• ATP is vital for both myosin activity and calcium ion regulation, highlighting the energy-intensive nature of muscle function.

This quiz explores the role of myosin in muscle contraction and how bacteria can exploit the host actin cytoskeleton for invasion. You'll learn about the dynamics of the actin cytoskeleton and its implications in human diseases caused by mutations. Test your understanding of these critical biological processes.