cytoskeleton

• The death cap mushroom is responsible for a majority of mushroom poisonings worldwide
• The death cap produces two major groups of multicyclic peptide toxins: amatoxins and phallotoxins
• Phalloidin, one of the phallotoxins produced by the death cap mushroom, poisons cells by binding tightly and specifically to actin filaments of the cytoskeleton
• Colchicine, isolated from the autumn crocus, is used to treat joint pain and gout
• Colchicine results in a metaphase arrest in cells by binding to tubulin, preventing the assembly of microtubules
• Taxol, isolated from the Pacific yew tree, interferes with the normal function of microtubules during cell division
• The cytoskeleton is an intricate network of protein filaments that extends throughout the cytoplasm of eukaryotic cells
• The cytoskeleton provides an architectural framework for the cell and is important during cell division, cell movement, cell signaling, and cell adhesion
• Microtubules determine the positions of organelles, direct intracellular transport, and form the mitotic spindle for chromosome segregation during cell division
• Actin filaments determine the shape of the cell's surface and are necessary for whole-cell locomotion
• Intermediate filaments provide mechanical strength in cells
• The cytoskeleton enables cells to assume and maintain complex shapes, plays important roles in cell movement and division, and moves membrane-bounded organelles within the cytosol
• Microtubules are hollow, tubular structures assembled from the protein tubulin and function in diverse activities such as cell support and material movement within cells
• Microtubules can form as singlets, doublets, or triplets, and are polarized structures built from αβ-tubulin dimers
• Microtubules are assembled from microtubule organizing centers (MTOCs) and are involved in diverse cellular activities
• The centrosome in animal cells is associated with centrioles and pericentriolar material, and serves to nucleate the growth of microtubules
• Kinesins move towards the positive end of microtubules, while dyneins move towards the negative end, both using ATP hydrolysis for movement
• Cilia and flagella are microtubule-based extensions of the plasma membrane found in many protozoan and animal cells
• The core of cilia and flagella, the axoneme, contains an array of microtubules that run longitudinally through the organelle
• Eukaryotic cilia and flagella contain long doublet microtubules bridged by dynein motors, allowing for ciliary beat in a whiplike fashion
• Ciliary beat:

  • Motile cilia beat in a whiplike fashion to move fluid over the surface of a cell or propel single cells through a fluid
  • A cilium beats by performing a repetitive cycle of movements, consisting of a power stroke followed by a recovery stroke
  • Cilia on the surface of a ciliated protozoan beat in metachronal waves
• Flagella propel:

  • Flagella propel a cell through fluid using repetitive wavelike motion
  • Flagella that propel sperm and many protozoa are usually longer than cilia
  • Designed to move the entire cell rather than moving fluid across the cell surface
  • Flagella propagate regular waves along their length, propelling the attached cell along
• Actin filaments (microfilaments):

  • Microfilaments are polymers of the protein actin organized into functional bundles and networks by actin-binding proteins
  • Important in organizing the plasma membrane and giving shape to surface structures such as microvilli
  • Can provide mechanical support or serve as tracks for ATP-powered myosin motor proteins
  • Actin-binding proteins control the behavior of actin filaments in vertebrate cells
• Intermediate filaments:

  • Form a strong, durable network in the cytoplasm of the cell
  • Found in the cytoplasm of most animal cells, typically forming a network throughout the cytoplasm
  • Often anchored to the plasma membrane at cell-cell junctions called desmosomes
  • Intermediate filament monomer consists of an α-helical central rod domain with unstructured terminal domains at either end
• Structure of the skeletal muscle sarcomere:

  • Skeletal muscles consist of muscle fibers made of bundles of multinucleated cells
  • Each cell contains a bundle of myofibrils consisting of thousands of repeating contractile structures called sarcomeres
  • Sarcomeres exhibit a characteristic banding pattern, giving the muscle fiber a striped or striated appearance
• Sliding of myosin II along actin filaments causes muscles to contract:

  • In the presence of ATP and Ca2+, myosin heads walk toward the ends of the thin filaments, shortening the sarcomere
  • Actin and myosin filaments slide past each other during contraction, shortening the sarcomere
  • Myosin heads drive the sliding motion walking toward the plus ends of the adjacent actin filaments
• The sliding-filament model of contraction in skeletal muscle:

  • In the relaxed state, thick myosin and thin actin filaments are arranged differently compared to the contracted state
  • Myosin heads extending from the thick filaments walk toward the ends of the thin filaments in the presence of ATP and Ca2+
  • The movement of myosin pulls actin filaments toward the center of the sarcomere, shortening its length in the contracted state
• The myosin superfamily in humans:

  • About 40 myosin genes in the human genome, 9 in Drosophila, and 5 in budding yeast
  • Bioinformatic analysis indicates about 20 distinct classes of myosins have evolved in eukaryotes
  • Mutations in genes encoding myosins can be linked to certain conditions
• Distinct modes of cell migration rely on the actin cytoskeleton:

  • While some cells use microtubule-based cilia or flagella to swim, many cells undergo crawling movements relying on the actin cytoskeleton
  • Cell migration depends on the actin-rich cortex beneath the plasma membrane
  • During embryogenesis, individual cells migrate to specific locations and epithelial sheets move coordinately
• Actin associates with myosin to form contractile structures:

  • Myosins bind to and hydrolyze ATP, providing energy for movement along actin filaments
  • Myosin-I has a single globular head that attaches to an actin filament and a tail that attaches to another molecule or organelle in the cell
  • Myosin-II assembles into bipolar filaments with heads exposed at the ends