Lecture 17 - Cytoskeleton_ muscles.pdf

Cytoskeleton: muscles Lecture 16 BIOL2020 Nicanor ~200 wing beats per second Michael H. Dickinson “The horse in motion” Eadweard Muybridge, 1878 Actin subunits assemble head-to-tail to form a tight, right-handed helix, forming a structure about 8 nm wide called filamentous or F-actin A myosin...

Cytoskeleton: muscles Lecture 16 BIOL2020 Nicanor ~200 wing beats per second Michael H. Dickinson “The horse in motion” Eadweard Muybridge, 1878 Actin subunits assemble head-to-tail to form a tight, right-handed helix, forming a structure about 8 nm wide called filamentous or F-actin A myosin II molecule is composed of two heavy chains and four light chains. Dimerization occurs when the two α helices of the heavy chains wrap around each other to form a coiledcoil. Each myosin head binds and hydrolyzes ATP, using the energy of ATP hydrolysis to walk toward the plus end of an actin filament In skeletal muscle, these tail–tail interactions form large, bipolar thick filaments that have several hundred myosin heads, oriented in opposite directions at the two ends Skeletal muscle cells (also called muscle fibers) are big multinucleated cells form by the fusion of many muscle cell precursors Overview of the skeletal muscle architecture Vertebrate Sarcomere (TEM) Luther, 2002 Lemke, 2019. Mech Dev. Each sarcomere is formed from a miniature, precisely ordered array of parallel and partly overlapping thin and thick filaments A myofibril is a cylindrical structure 1–2 μm in diameter that is often as long as the muscle cell itself. It consists of a long, repeated chain of tiny The sliding filament theory ~1950: a muscle fiber contracts when myosin filaments pull actin filaments closer together and thus shorten sarcomeres within a fiber ● ● ● Actin filaments slide on myosin filaments. The A-band (black) does not change The I-band (white) disappears Sarcomere shortening is caused by the myosin filaments sliding past the actin thin filaments, with no change in the length of either type of filament The myosin and actin filaments are packed together with almost crystalline regularity. The thin filaments are composed of actin and associated proteins, and they are attached at their plus ends to a Z disc at each end of the sarcomere. Thick filaments are anchored at the M line α-actinin holds actin thin filaments together in a regularly spaced bundle. The actin filament plus ends are anchored in the Z disc, which is built from CapZ CP-ɑ CP-𝛃 https://doi.org/10.1038/s41467-021-25682-5 Titin acts as a molecular spring, with a long series of immunoglobulin-like domains that can unfold as stress is applied to the protein. Titin keeps the thick filaments poised in the middle of the sarcomere Nebulin maintains the length and the stability of the thin filament and consists almost entirely of a repeating 35-amino-acid actin-binding motif.. Part 2: contraction regulation A Sudden Rise in Cytosolic Ca2+ Concentration Initiates Muscle Contraction The signal from the nerve triggers an action potential in the muscle cell plasma membrane, and this electrical excitation spreads swiftly into a series of transverse tubules, or T tubules—that extend inward from the plasma membrane around each myofibril. When the incoming action potential activates a Ca2+ channel in the T-tubule membrane, it triggers the opening of a Ca2+-release channel in the closely associated sarcoplasmic reticulum membrane Ca2+ flooding into the cytosol then initiates the contraction of myofibrils through the Troponin complex and Tropomyosin ( ● ● troponin Tropomyosin Molecular Landscapes by David S. Goodsell tropomyosin is an elongated protein that binds along the groove of the actin filament helix. The other is troponin, a complex of three polypeptides In a resting muscle, the troponin complex pulls the tropomyosin into a position along the actin filament that interferes with the binding of myosin heads. When the level of Ca2+ is raised, troponin C—which binds to Ca2+—causes troponin I to release its hold on actin. The increase in Ca2+ concentration is transient because the Ca2+ is rapidly pumped back into the sarcoplasmic reticulum by an ATP-dependent Ca2+-pump Stretch activation is an intrinsic length-sensing mechanism that allows muscles to function with an autonomous regulation (bypassing calcium). Scott B Williams @EntomoLogical Muscle Structure myofibrils sarcomeres Z disc M line alpha actinin CapZ Titin Muscle Function T-tubules Sarcoplasmic reticulum Troponin complex Tropomyosin Serca pump Stretch activation https://youtu.be/F2XfnNbaB98?si=HqbhvVJ5YP2FdXOb James Spudich: A brief history of muscle biology