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    2.17.2010 2.17.2010 Document Transcript

    • 2.17.2010 – Cytoskeleton<br />Continuation of cellular respiration<br />
      • Diseases Associated with Mutations in cellular Respiration
      • Leigh Syndrome – decreased activity in cytochrome c oxidase
      • Brain tissue loss and muscular deficiency
      • terminal
      • Complex II deficiency
      • Short stature, seizures, mild swelling in and around the brain, encephalopathy
      • Not terminal
      • Beriberi
      • Lack of thiamine, vitamin B1
      • Decreased activity in pyruvate dehydrogenase and alpha-ketogluterate dehydrogenase (regulatory enzyme in krebs cycle)
      • Can take thiamine supplements
      • w/out B1, krebs cycle can work as well
      • nervous system disorders.
      • The cytoskeleton regulates
      • cellular mitosis
      • meiosis
      • cell motility (entire cell)
      • Motility and trafficking of proteins, organelles, RNA in the cell
      • Cell-cell adhesion
      • Counterparts in Bacteria – slide 2
      • Microtubules (formed by dimmers of the tubulin monomers) – counterpart in bacteria, FtsZ gene
      • cell division
      • Actin (microfilaments) – counterpart in bacteria, MreB
      • DNA segregation
      • Intermediate Filaments – counterpart in bacteria Crescentin
      • Maintaining shape
      • Properties of Microtubules, Microfilaments, and Intermediate Filaments
      • Microtubules
      • Growing and shrinking end
      • Formed by the dimer tubulin monomer
      • Function
      • Organized into structure that allows for a specific motility
      • Axoenemal
      • Whip-like movement such as sperm cells.
      • Make up much of the cytoplasm to make a dense environment
      • Chromosomal movement
      • Microfilaments/Actin filaments
      • Actin is smallest
      • Makes microfilaments
      • Link g-actin together non-covalently
      • Cell division
      • Amoeboid Movement
      • Cytosol of an amoeba is a gel, or plasma gel. The gel is converted to plasmasol, so it’s more fluid and the movement is more fluid
      • If you have a structure like an amoeba, the cytosol is more gel like than water, so plasma gel. For movement, the gel is converted to plasmasol, so it’s more fluid and the movement is more fluid, which tends to create a force or pressure along membrane as force is mediated
      • Intermediate Filaments – structure and support for cells
      • No polar sides! So very good at structural support system for cells.
      • Structural support
      • Maintain shape
      • Nuclear lamina
      • Just on the inside of nuclear envelope
      • Strengthening of nerve cells
      • Desmin helps maintain muscle cell shape when undergoing mechanical movement
      • Not as dynamic as microfilaments and microtubules
      • Rope-like structures
      • Cytoplasmic filament (slide 3) have concentrated areas in sites called desmosomes, which provide linkage between cells to hold them. Proteins make desmosomes, but the filaments hold the cells together by interacting with desmosomes. They don’t hold directly to cells, but link to one another to hold cells together in a tissue structure.
      • Nuclear lamins (blue area around nucleus)
      • Can help regulate what goes in and out of nucleus
      • (Slide 4) 8-12nm. Begins with assembly of alpha helix monomer, made of four alpha helices with 3 regions that separate the monomer itself. 310-318 amino acids, all of which are hydrophilic. At the end, amino and carboxy terminus, hydrophobic, tend to be regions that associate with other types of proteins.
      • Coiled-coil dimers come together in a staggered position for amino and carboxy terminus do not overlap, and this allows the tetramers to pack together at the heads, through non-covalent bonding. Eight tetramers are brought together and form a rope-like structure.
      • Classes of Intermediate Filaments
      • Specificity of intermediate filaments can help us identify cells and localize the filaments in the cell.
      • Slide 6 is trying to show intermediate filaments at the desmosomes
      • Epidermolysis bullosa simplex
      • K14 gene generates two types of Keratin, class I and II.
      • Any amount of stretching will rip epithelial cells apart and can lead to blistering.
      • Neurofilament diseases
      • Epidermalisis – lysing of the epidermis below cymplex
      • Mutation in keratin – k14 gene – that is responsible for generating two classes of keratin, I and II, when they can’t function they can’t hold selves together, so blistering wounds can be found on the skin.
      • Lou Gerhig’s Disease (ALS – Armyotropic Lateral Sclerosis)
      • NF-H, Peripherin
      • Protein that is mutated as well as neuro fiaments
      • Sometimes not terminal, depends of genetics of person
      • Cardiomyopathies – desmoplakin, which can induce heart failure.
      • Nuclear Lamins is formed by lamin proteins
      • Polarized cell.
      • Found under the nuclear envelope, and separating the chromatin from the envelope.
      • Laminopathies
      • Lipodystrophy
      • Fat cells are abnormally deposited
      • Heart attacks, high BP etc
      • ADLD – Autosomal Dominant Leukodystrophy
      • Loss of myelin mutation in Lamin A
      • Can lead to loss of motor control/paralysis
      • Assembly of microtubules (Slide9)
      • Alpha and beta dimers
      • Oligomer
      • Nucleation site
      • 13 protofilaments form a microtubule when they close
      • once closed, either end can be an end where dimmers come on or off so either end can be plus or minus end.
      • Either end can grow and shrink
      • Line up so plus and minus ends are in same region of the cells, - at nucleus, plus at end of axon where growing takes place.