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.