Cytoskeleton

• The cytoskeleton is a 3-D system of fibers running through the cytosol, first discovered in the 1950's with electron microscopy
• The cytoskeleton is important in cell mobility, cell division, cell shape, movement of organelles and chromosomes
• Three main types of cytoskeletal fiber

  • Microfilaments
  • Microtubules
  • Intermediate filaments
• Microfilaments


  About 7 nm in diameter and are composed of two actin chains twisted around each other, with a variety of structural and locomotor functions
• Microtubules


  Straight hollow rods 25nm in diameter and up to 20 microns long, constructed from globular proteins called Tubulins
• Intermediate filaments


  1. 12nm in diameter and are made up of a diverse group of proteins, tend to be permanent fixtures and are important in maintaining cell shape and organelle position
• Actin filaments


  • Present in all eukaryotic cells
  • Functions include muscle contraction, cell movement and migration, cell separation during cytokinesis, cell shape, and structural roles like formation of microvilli
  • Composed of actin which is a globular protein (G actin) that polymerizes to form insoluble filamentous actin (F actin), a double right-handed helical molecule
  • Most animal cells have a network of actin filaments just below the cell surface termed the Cell Cortex, which supports the plasma membrane and facilitates cell movement
• Actin polymerization

  1. G-actin assembles into long, helical F-actin polymers

  2. ATP holds together the two lobes of the actin monomer

  3. Many movements are driven by actin polymerization
• Actin polymerization drives

  • White blood cell transmigration
  • Cellular extensions
• Actin and myosin II have essential roles in cytokinesis
• Myosins


  Use energy derived from ATP hydrolysis to "walk" along actin filaments, with contraction or transportation roles
• Phalloidin, a toxin, binds to F-actin preventing disassembly and can be used to stain actin when attached to a fluorescent tag
• Tubulin dimers

  The building blocks of microtubules, appearing as hollow rods about 25nm in diameter under the TEM
• Microtubules


  • There are two main types - axonemal (highly organized and stable, found in cilia/flagella/basal bodies) and cytoplasmic (more dynamic and loosely organized, found in the cytoplasm)
  • cytoplasmic Involved in maintaining cell shape, cell movement, transport of vesicles, and chromosome separation during cell division
  • Act as tracks along which vesicles and small particles can move via the motor proteins kinesin and cytoplasmic dynein
• Microtubule-based transport


  Kinesin moves cargo toward the (+) end of microtubules (anterograde), while most dyneins transport cargo towards the (-) end of microtubules (retrograde), utilizing the energy from ATP hydrolysis
• Microtubule-binding drugs like taxol are used to treat diseases like cancer by preventing microtubule disassembly and therefore cell division in cancer cells
• Cilia and flagella

  • Consist of a core of axonemal microtubules ensheathed in an extension of the plasma membrane, with a 9+2 arrangement of microtubules
  • Dynein contracts at the expense of ATP, forcing the microtubule doublets to move relative to each other, causing the flagella/cilia to bend
  • Crosslinking proteins prevent the doublets from sliding past each other
• Cilia are shorter (2-20µm) and more numerous than flagella (10-200µm), but both have the same structure
• Intermediate filaments

  Fibrous subunits of keratin proteins coiled together, 8-12nm in diameter
• Intermediate filaments


  • Tend to be permanent fixtures, important in maintaining cell shape and organelle position
  • Involved in cell junctions
• Types of intermediate filaments

  • Keratin (found in epidermis, causing Epidermolysis Bullosa Simplex when defective)
• The mitotic apparatus in a metaphase mammalian cell contains microtubules
• Functions of the cytoskeleton

  • muscular movement to transport of molecules through out the cell
  • normal embryonic embryonic development
• Function of intermediate filament

  cell junction

  maintaining cell shape

  anchorage of nucleus and organelles

  formation of nuclear lamina
• Microtubules subunits

  alpha and beta
• Structure of microtubules

  hollow tubes, the wall consists of 13 columns of tubulin molecules

  Diameter of 25nm with a lumen of 15nm
• Function of microtubules

  • maintenance of cell shape
  • cell motility
  • chromosome movement in cell division
  • organelle movements
• Defect in keratin 14 gene leads to?

  epidermolysis bullosa simplex