CELL STRUCTURE EXAM 3CHAPTER 17: The CytoskeletonThe cytoskeleton is an intricate network of protein filaments that extends throughout the cytoplasm andallows cells to adopt a variety of shapes, organize its components, and interact mechanically with the environment. This is most prominent in the large and structurally complex eukaryotic cells, acting as the “bones” and “muscles”. Without the cytoskeleton, wounds would never heal, muscles would be useless, and sperm would never reach the egg. The cytoskeleton controls the location of the organelles that conduct these specialized functions, in addition to providing the machinery for transport between them. There are three types of filament: intermediate filaments (mechanical strength), microtubules (propelling motile cells), and actin filaments (motive force). I. Intermediate Filamentsa. Overviewi. Displaying great tensile strength, their main function is to enable cells to withstand the mechanical stress that occurs when cells are stretched. These are the most durable filaments and when cells are treated with concentrated salt solutions and nonionic detergents, they survive while the rest of the cytoskeleton is destroyed. ii. Third filament type to be discovered; “boring” Intermediate filaments form a network throughout the cytoplasm, anchored to the plasma membrane at cell-cell junctions. They also make up the nuclear lamina, underlying and strengthening the nuclear envelope. a. Intermediate filaments are strong and rope-like. a. Subunits of these filaments are elongated fibrous proteins, each composed of an N-terminal globular head, a C-terminal globular tail, and a central elongated rod domain. This rod domain consists of an extended helical region that enables pairs of filament proteins to form stable dimers by wrapping around each other in a coiled-coil configuration. Two of these coiled-coil dimers then associated to form a tetramer and the tetramers bind to one another. This bonding is carried out via non-covalent forces. These rod domains are fairly consistent in structure and sequence while the heads and tails vary greatly in both size and sequence. i. Analogy from class: curly hair is held together in tight ringlets by hydrogen bonding. Showering involves heat, as well as chemical and mechanical stress from shampoo that denatures the hydrogen bonds. This is why curly hair straightens after showering. b. Intermediate filaments strengthen cells against mechanical stress. By stretching and distributing the effect of locally applied forces, intermediate filaments keep cells and their membranes from breaking in response to mechanical shear. a. Four classes: i. Keratin filaments in epithelial cells 1. Found in cytoplasm 2. Most diverse class of intermediate filaments (makes sense because every body system contains epithelial lining) 3. Typically span the interiors of epithelial cells from one side of the cell to the other 4. Connect to filaments on adjacent cells by anchoring their heads to desmosomes (cell-cell junctions)a. Associate with other cell components through their globular head and tail domains, which project from thesurface of the assembled filament b. This anchoring gives the filaments a cabling effect and allows them to achieve high tensile strengthc. Facilitates the distribution of stress that occurs when skin is stressed i. Mutations in keratin: Epidermolysis bullosa simplex1. Mutations in keratin genes interfere with the formation of keratin filamentsin the epidermis. Mutated protein produces abnormal intermediate filaments. 2. Skin blistering and lesions occur due toimproper anchorage between cells, making the skin highly vulnerable to mechanical injury. ii. Vimentin in connective-tissue cells1. found in cytoplasmiii. Neurofilaments in nerve cells 1. found in cytoplasm iv. Nuclear lamins strengthening the nuclear membranes of all animal cells 1. Found in cell nucleus b. Stabilizing accessory proteins, like plectin, reinforce the filaments by holding bundles of filaments together and by linking them to microtubules, actin molecules, and to adhesive structures on the desmosomes. i. Plectin mutations cause damaging effects because their cross-linking action is required to provide cells with the strength they need to withstand mechanical stress. 1. Epidermolysis bullosa simplex a. Caused by disruption of keratin in the skin 2. Muscular dystrophy a. Caused by disruption of intermediate filaments in the muscle3. Neurodegeneration a. Caused by disruption of neurofilaments c. The nuclear envelope is supported by a meshwork of intermediate filaments called thenuclear lamina. a. Lamins: intermediate filament proteins that make up the lamina b. Contrasted to stable cytoplasmic intermediate filaments because they dissemble and re-form at each cell division when the nuclear envelope breaks down and re-forms during mitosis. i. Disassembly and reassembly of the nuclear lamina are controlled by the phosphorylation and dephosphorylation of the lamins by protein kinases.1. Phosphorylation results in a conformational change that weakens the binding between tetramers, causing the filament to fall apart. 2. Dephosphorylation at the end of mitosis causes the lamins to reassemble into each daughter cell ii. Defects in lamins 1. Progeria: rare disorders that cause affected individuals to appear to age prematurely a. Children have wrinkled skin, lose their teeth and hair, and often develop severe cardiovascular disease by the time they reach their teens b. Possibly due to impaired cell division due to nuclear instability II. Microtubules:a. Overview of featuresi. Long, relatively stiff, and hollow tubes of protein that can rapidly disassemble and reassemble.ii. They grow out from the centromere near the center of the cell, extending outward to create a system of tracks within the cell. The system is responsible for anchoring membrane-enclosed organelles within the cell and guiding for transport. 1. Vesicles, organelles, and other cell components are moved on these tracks. iii. Mitotic spindle formation (motility) 1. When a cell enters mitosis, the cytoplasmic microtubules disassemble and then reassemble into the mitotic spindle 2. Mitotic spindle provides the machinery that will segregate the chromosomes equally into the two daughter cells just before a cell divides. iv. Permanent structure formation 1. Microtubules can form permanent structures like cilia and flagella, hair-like structures that extend on the