Cytoskeleton

[Audio] Cytoskeleton is actually the framework of a cell. In other words it is a thin network of filaments on which the organelles of a cell are suspended..

[Audio] This video describes the different types of cytoskeleton, what are they made of and their functions. The interaction of the cell membrane and the cytoskeleton is also described in this video..

Cytoskeleton. The cytoskeleton provides a structural framework for the cell, serving as a scaffold that determines cell shape, the position of organelles and the general organization of cytoplasm..

Structure. Microfilaments Intermediate filaments Microtubules.

Microfilaments. Actin filaments – flexible fibres Diameter – 6-8 nm; length – several micrometers Organised in three-dimensional network with the properties of semisolid gel Function: Maintains cell shape (tension-bearing elements) Muscle contraction Cell division (cleavage furrow formation) Cell motility.

Molecular Structure of microfilaments. Assembly: Formed by head-to-tail polymerization of actin monomers into a helix. Actin binding proteins – Regulates assembly and disassembly..

Drugs affecting microfilament function. Cytochalasin Phalloidin - Prevents microfilament assembly.

Myofilaments. Microfilaments present in Striated muscles. Muscle fibres are made of Myofibrils which are composed of myofilaments. Myofilaments are composed of Actin filaments (thin filaments) - 6-7 nm F (fibrous) actin Tropomyosin Troponin - Tn-A , Tn-T, Tn-C 2. Myosin filaments (thick filaments) – 12-16 nm Contractile filaments - When myofibril shortens muscle contracts..

Molecular structure of myofilaments.

Clinical Implication. Mutations in myosin isoforms – blindness, deafness and familial hypertrophic cardiomyopathy . Duchenne Muscular Dystrophy – Autosomal recessive disorder, where the gene that codes for dystrophin is defective, resulting in muscle degeneration and finally death..

Microvilli. Specialized structure composed of microfilaments. Tiny, finger-like processes that projects from the luminal surface of absorptive cells. Diameter – 0.1 µm Thin, superficial layer is termed as striated border or brush border. Functions: Intestinal Villi – Absorption Proximal tubule of kidney - Mechanosensors.

Molecular structure of microvilli. Made of bundle of cross-linked microfilaments. Microfilaments extends down the central core of microvillus Coated by Glycocalyx.

Clinical implication. Destruction of microvilli - malabsorption of nutrients and persistent osmotic diarrhea. Microvillus Inclusion Disease - inherited disease characterized by defective microvilli and presence of cytoplasmic inclusions of the cell membrane . Microvillous atrophy - Congenital lack of microvilli in the intestinal tract (a rare, fatal condition found in new-born babies).

Intermediate filaments. Polymers of 50 different proteins that are expressed in various cells. Diameter – 10 nm Functions: Mechanical support to tissues. Maintenance of cell shape Anchorage of nucleus and certain other organelles Formation of nuclear lamina.

Molecular structure of intermediate filaments. Dimers of 2 polypeptide chains Coiled structure tetramers Protofilaments Intermediate filaments (Ropelike structure).

Classification. Class 1 Acidic keratin 40-60 kda Epithelia(Tonofilaments) Class 2 Neutral or basic keratin 50-70 kda Epithelial cells Class 3 Vimentin 54 kda Fibroblasts, WBC and others Desmin 53 kda Muscle cells Glial fibrillary acidic protein 51 kda Glial cells Peripherin 57 kda Peripheral neurons Class 4 Neurofilament proteins (NF-L, NF-H, NF-M, alpha internexin) 67 kda Neurons Class 5 Nuclear lamin 60-75 kda Nuclear lamina of all cell types Class 6 Nestin 200 kda Stem cells, especially CNS.

Clinical implication. Epidermolysis bullosa simplex (EBS) - mutations in the genes encoding keratin 5 or keratin 14. White sponge nevus – hereditary autosomal dominant disease due to mutations in keratin 4 and 13. Keratin expression is helpful in determining epithelial origin in anaplastic cancers. Tumors that express keratin-carcinomas, thymomas, sarcomas and trophoblastic neoplasms ..

Microtubules. Rigid hollow rods Diameter – 20-25 nm Functions: Maintains cell shape For cell motility Transport of organelles Forms spindle fibers for separation of chromosomes during mitosis. Major structures – Cilia and flagella..

Molecular structure of microtubules. Assembled in Microtubule – organising center or centrosomes . Made of tubulin dimers – Alpha and Beta tubulins by reversible polymerization. Consists of 13 linear protofilaments assembled around a hollow core..

Drugs that affect microtubule function. Colchicine Vinblastine Vincristine.

Cilia. Microtubule projections of the plasma membrane on the surface. Diameter – 0.25 µm, Length – 10 µm. Unidirectional movement. Functions: To move fluid or mucus over the surface of the cells..

Ciliogenesis. Starts in cylindrical structures called centriole organisers Immature centrioles (Procentrioles) assemble around centriole organisers Multiple centrioles produce cilia Migrate below the luminal border Becomes basal bodies Distal end – Cilium Lateral part – basal foot Proximal end – Anchoring rootlets.

Flagella. A slender threadlike structure, especially a microscopic whiplike appendage that enables many protozoa , bacteria and spermatozoa to swim..

Molecular Structure of cilia and flagella. Made of axoneme which is composed of microtubules and proteins. Microtubules are arranged in 9+2 pattern. Outer tubules – connected to central pairs by radial spokes and to each other by nexin. Movement: Sliding of microtubules driven by action of dynein motors..

Clinical implication. Absence of cilia in females – ectopic pregnancy Ciliary defects due to genetic mutations - ciliopathies Primary ciliary dyskinesia (immotile ciliary syndrome) – autosomal recessive disorder, causing defect in the action of cilia lining respiratory tract, fallopian tube and flagella of sperm..

Cell membrane. The outermost component of the cell, separating the cytoplasm from its extracellular environment, is the plasma membrane ( plasmalemma ). Thickness – 8 to 10 nm Functions : Selective barrier - transports specific molecules. Keeps the intracellular environment constant. Recognition and regulatory functions..

Trilaminar structure Composed of -phospholipids - Phosphotidylcholine Phosphatidyl ethanolamine Phosphatidyl serine Sphingomyelin Phosphotidyl inositol Cholesterol Proteins - Integral proteins and peripheral proteins Carbohydrate – Glycolipids and Glycoproteins.

Clinical implication. Abnormalities of erythrocyte membrane – Hereditary spherocytosis , hereditary elliptocytosis , hereditary pyropoikilocytosis , hereditary stomatocytosis ..