L13 Cytoskeleton Elements & Cell Division PDF

13 Cytoskeletal microtubules & Microfilaments & motility ILOs By the end of this lecture, students will be able to 1. Correlate the molecular organization of microtubules to its dynamic nature. 2. Interpret structural adaptation of MT to their function. 3...

13 Cytoskeletal microtubules & Microfilaments & motility ILOs By the end of this lecture, students will be able to 1. Correlate the molecular organization of microtubules to its dynamic nature. 2. Interpret structural adaptation of MT to their function. 3. Correlate the relevant motor proteins in cell trafficking to MT. 4. Appraise the importance of microtubules as a target for drug action. 5. Correlate molecular structure of actin to its function. Cytoskeleton The cytoplasm of animal cells contains a cytoskeleton, an intricate three-dimensional meshwork of protein filaments that are responsible for the maintenance of cell shape (Fig 1). Additionally, the cytoskeleton is an active participant in cellular motion, whether of organelles or vesicles within the cytoplasm, regions of the cell, or the entire cell. The cytoskeleton has three components: thin filaments (microfilaments), intermediate filaments, and microtubules. Fig. 1 The cytoskeleton Microtubules Microtubules (MTs) are long, straight, hollow structures that act as intracellular pathways. The centrosome is a region close to the nucleus that houses the centrioles, as well as several hundred ring-shaped γ-tubulin ring complex molecules that act as nucleation sites for microtubules (fig. 2). Microtubules are dynamic structures that frequently change their length by undergoing growth spurts and then becoming shorter; both processes occur at the plus ends (oriented away from the nucleus), so that the average half-life of a microtubule is only about 10 minutes (fig. 2-B). Molecular structure of MTS Each microtubule consists of 13 parallel protofilaments composed of heterodimers of the globular 1  polypeptide α- and β-tubulin subunits. Fig. 2 Molecular structure of MTs A B Functions of MTs Provide rigidity and maintain cell shape. Regulate intracellular movement of organelles and vesicles. Establish intracellular compartments. Provide the capability of ciliary and flagellar (tail of the sperm) motion. During cell division, rapid polymerization of existing, as well as, new microtubules is responsible for the formation of the mitotic spindle. Clinical correlation The dynamic process of microtubule formation is disrupted by some drugs which can have different clinical effects on cellular functions e.g. Colchicine: By binding to the tubulin molecules in leukocytes, colchicine prevents its polymerization into microtubules. It thus interferes with leukocyte migration, phagocytosis and further release of inflammatory mediators, and this is the basis for its anti-inflammatory effect in acute gouty arthritis (Joint inflammation due to precipitation of urate crystals). Microtubule-associated proteins Microtubule-associated proteins are motor proteins that assist in the translocation of organelles and vesicles inside the cell. 2  Their primary functions are to prevent depolymerization of microtubules and to assist in the intracellular movement of organelles and vesicles. Movement along a microtubule occurs in both directions and is toward both the plus end and the minus end. The two major families of microtubule motor proteins, the MAPs dynein and kinesin, bind to the microtubule as well as to vesicles and organelles In the presence of ATP, dynein moves the vesicle toward the minus end of the microtubule. Kinesin effects vesicular (and organelle) transport in the opposite direction, toward the plus end. Centrioles Centrioles are small, cylindrical structures composed of nine microtubule triplets; they constitute the core of the microtubule organizing center or the centrosome. They are paired structures, arranged perpendicular to each other, and are located in the microtubule organizing center, the centrosome, in the vicinity of the Golgi apparatus. Functions of the centriole The centrosome assists in the formation and organization of microtubules as well as in its self- duplication before cell division. During cell division, centrioles are responsible for the formation of the spindle apparatus. Additionally, centrioles are the basal bodies that guide the formation of cilia and flagella (motile cell processes). 3  Fig. 5 Cilia & Flagellum Actin Filaments (microfilaments) Thin filaments (microfilaments) are composed of two chains of globular subunits (G-actin) coiled around each other to form a filamentous protein, F-actin. Thin filaments are 6-nm thick and possess a faster-growing plus end and a slower-growing minus end. Functional forms of actin 1. Contractile bundles: Their actin filaments are arranged loosely, parallel to each other, with the plus and minus ends alternating in direction. They form cleavage furrows (contractile rings) during mitotic division. Movement of organelles and vesicles within the cell. Cellular activities, such as exocytosis and endocytosis, as well as the extension of filopodia and cell migration (fig. 6-D). 2. Gel-like networks: provide the structural foundation of much of the cell cortex (fig. 6-C). 3. Bundles: form the core of microvilli (apical cell projections) (fig. 6-A). 4. Focal points: points of contact between the cell and the extracellular matrix (fig 6-B). 4  Fig. 6- Functional forms of actin A B Focal points F C D 5