Myosin And Myosin Function And Its Effect On A Huge Number Of Diseases

Contractility of ASM requires an increased levels of intracellular Ca2+. When surface receptors are not activated, Ca2+ levels are low. Upon activation of these cell surface receptors by contractile agonists e.g. acetylcholine, serotonin and histamine, intracellular Ca2+ increases causing a contraction (9). Smooth muscle cell contraction is controlled by both receptor and mechanical activation of proteins actin and myosin and also changes to membrane potential.

-Sarcoplasmic Reticulum (SR) then releases Calcium which binds to troponin in the thin filament, exposing myosin-binding sites;

ATP is required to break the attachment of actin to the myosin head. At death, calcium ions leak out of the SR

Smooth muscle contraction occurs when calcium is present in the smooth muscle cell and binds onto calmodulin to activate myosin light chain kinase (Wilson et al., 2002). Phosphorylation of myosin light chains result in myosin ATPase activity thus cross-bridge cycling occurs causing the muscle to contract (Horowitz et al., 1996). There are two known models of excitation and contraction in smooth muscle, electromechanical coupling (EMC) and pharmomechanical coupling

Cytoplasmic streaming is the organised flow of the cytoplasm and its constituents within a living cell (Shimmen et al., 2004). Organelles and important molecules move through the cytosol along the structure of the cytoskeleton (actin filaments and microtubules) with the aid of myosin I, an actin-binding motor protein that plays a part in various cell functions including cell motility and endocytosis (Flavell et al., 2008). Actin microfilaments (F-actin) are the thinnest filaments of the cytoskeleton,

Introduction: According to the “Human Physiology Laboratory Manual “,BIOL 282 ,page 31 , the reason of performing this experiment is to learn how the muscle contraction occurs based on the molecular level and what kind of factors are involved .As a matter of fact, skeletal muscles contain a lot of nuclei because of the cell fusion while being developed and are made of cylindrical cells that have myofibrils. The myofibrils contain sarcomeres and the

For muscle to contract, actin and myosin filaments need to slide past each other, causing the sarcomere to shorten in length . Each myosin filament has a protruding bulbous head, which can bind with the binding sites on the

Myofibrils are made up of long proteins that include myosin, titin, and actin while other proteins bind them together. These proteins are arranged into thin and thick filaments that are repetitive along the myofibril in sectors known as sarcomeres. The sliding of actin and myosin filaments along each other is when the muscle is contracting. Dark A-bands and light I-bands reappear along myofibrils. The alignment of myofibrils causes an appearance of the cell to look banded or striated. A myofibril is made up of lots of sarcomeres. As the sarcomeres contract individually the muscle cells and myofibrils shorten in length. The longitudinal section of skeletal muscle exhibits a unique pattern of alternating light and dark bands. The dark staining, A-bands possess a pale region in the middle called the H-zone. In the middle of the H-zone the M-line is found, that displays filamentous structures that can join the thick filaments. The light-staining bands also known as I-bands are divided by thin Z-line. These striated patterns appear because of the presence of myofibrils in the sarcoplasm (IUPUI, 2016).

Pasternak C, Wong S, Elson EL. (1995). Mechanical function of dystrophin in muscle cells. The Journal of Cell Biology, 128(3), 355-361. doi:10.1083/jcb.128.3.355

Actin and myosin are contractile proteins that are essential for muscle contraction (Powers). A contraction is triggered by a series of events called the crossbridge cycle. In a muscle fiber, the functional unit of contraction is called a sarcomere (Powers). A sarcomere contains myofibrils, which consist of actin and myosin myofilaments. The sarcomere shortens when myosin heads and thick myofilaments form crossbridges with actin molecules and thin myofilaments. The formation of a crossbridge is initiated when calcium ions released from the sarcoplasmic reticulum bind to troponin. An action potential triggers this release of these ions. The binding of calcium ions causes troponin to change shape. Tropomyosin moves away from the myosin binding cites on actin, allowing the myosin head to bind actin and form a crossbridge. When ATP on the myosin head has not been hydrolyzed yet, the myosin head is inactivated, or in the uncocked position. The myosin head has to be activated before a crossbridge cycle can begin (Powers). This occurs when ATP binds to the myosin head and is hydrolyzed to Adenosine Diphosphate (ADP) and an inorganic phosphate. The enzyme that breaks this ATP down is called myosin ATPase, which is located on the myosin head. The energy from the hydrolysis activates the myosin head putting it into the cocked position. The activated myosin head binds to actin forming a crossbridge. Then inorganic

1.3: Is the lifespan extension observed in ykl∆ cells due to effects on actin cable stability? Here, the goal is to test whether reducing actin cable stability prevents the lifespan extension produced by deletion of Ykl. We will reduce actin cable stability by mutating tropomyosin. There are two tropomyosin isoforms in yeast, Tpm1 and Tpm2. Both isoforms localize to actin cables. However, Tpm1 stabilizes F-actin in actin cables. In contrast, Tpm2 regulates RACF by inhibiting the binding of myosin to actin within actin cables. Previous studies in mammalian cells indicate that mutations in the actin binding pocket of tropomyosin reduces their ability to bind to and stabilize F-actin. I will generate the same mutations in TPM1 and identify conditions that reduces actin cable abundance to wild-type levels in ykl∆ cells. Lastly, I will test whether restoring the wild-type actin cable levels in ykl∆ cells prevents the lifespan extension originally seen in ykl∆ cells.

Figure 4. We created a flow chamber in which kinesin was nonspecifically bound to a coverslip. As shown in (A), fluorescently-labeled microtubules were flowed in and the kinesin transported the microtubules. A sample timelapse set of images is shown in (B). None of the mutants were able to bind microtubules at our standard assay condition salt concentration of 50 mM NaCl. At lower salt concentrations, most L11 and L12 mutants had decreased velocities when compared to wildtype. However, P278L exhibited “rigor binding”, meaning kinesin was bound to microtubules, but there was no

actin “slid” past each other and neither filament changed in length. In 1957 Allan Huxley

Actin contains bound ATP is described by Straub and Feuer (1989); during polymerization to microfilaments, the nucleotide is hydrolyzed to ADP. Straub suggested that the transformation of ATP-bound actin to ADP-bound actin played a role in muscular contraction. The crystal structure of G-actin was solved by Kabsch and colleagues (1990). In the same year, a model for F-actin was proposed by Holmes and colleagues following experiments using co-crystallization with different proteins. In 2001 more clear structure was illustrated by

form of myosin ATP and are not very good at delivering calcium to the muscle