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Biochemistry, Medicine, Phase 1

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Term
Definition
Cytoskeleton   a network of protein filaments that extend throughout the cell  
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The cytoskeleton determines   cell shape and polarity; tissue structure; adhesion; cell movement; intracellular movement (of vesicles and of chromosomes)  
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Three classes of protein polymer (or filament)   actin, intermediate filaments, microtubules  
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Actin   microfilaments; composed of actin-binding proteins; comprises 5% total protein  
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Microtubules   composed of micro-tubule-associated proteins (MAPs)  
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Actin filaments (1)   called F-actin (filamentous actin or microfilaments); are polymers of individual actin proteins called G-actin (globular actin)  
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Actin monomers   G-actin (globular actin)  
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Actin filament (2)   polarised double helix; 13 actin subunits for every complete turn  
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Diameter of actin filament   7nm  
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Growth of actin filament   requires ATP to be bound to the actin monomer (G-actin); filaments are very dynamic (intermediate filaments are not); monomers can be added and removed from both ends of the polymer  
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G-actin adds more rapidly to   (+) end of the filament; once incorporated, ATP is hydrolysed to ADP  
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G-actin is removed more rapidly from   (-) end of the filament  
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Polymerisation of actin filament   when g-actin is ATP bound it can bind to the growing actin filament; not very stable over time; ATP eventually hydrolyses to ADP and will depolarise and come off at the negative end of the filament  
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Cell migration   happens a lot during embryogenesis but also adulthood; also pathogensis (metastasis); actin filaments turn over rapidly  
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Major function   mechanical support; cell shape changes and maintenance; cell motility  
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Actin-binding proteins   modulate polymerisation dynamics and function;  
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Membrane-attachment proteins   spectrin; bind to G-actin  
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Severing proteins   geisolin, severin; bind to F-actin  
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Cross-linkingproteins   transgelin; bind to F-actin  
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Capping proteins   prevent filament grown; bind to F-actin  
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Actin-sequestering proteins   bind to G-actin and prevent its polymerising;  
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Actin-bundling protein   alpha-actinin in muscle  
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Motor proteins   myosin in muscle; bind to F-actin  
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Side-binding proteins   interaction with other proteins; bind to F-actin  
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Intermediate filaments   polymer of individual intermediate filament proteins; 10nm in diameter; visible by electro microscope; not dynamic  
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Intermediate filament network   typically more dense around the nucleus; can extend into the periphery  
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Functions of intermediate filaments   used to anchor cells at some cell junctions; support nuclear structure; can act as diagnostic tools to identify foreign cells as they are expressed differently based on their different locations (e.g. cancer)  
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Intermediate filament names by cell type   keratin, vimentin, glial fibriallary acidic protein, neurofilamin  
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Mice lack neurofilaments (NF+/-)   reduces axon diameter  
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Formation of the intermediate filament polymer   intermediate filament protein (monomer) forms a helical dimer; two timers combine to form a tetrameter (the fundamental units of the IF); tetramers link in a staggered formation and end-to-end to form the filament  
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Tetramer   fundamental unit of the intermediary filament; formed from two helical dimers  
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Growth of an intermediate filament   slow, not dynamic; subunit exchange occurs throughout the length of the filament  
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Plectin   a protein that binds to intermediary filaments; these molecules link to IFs and to actin filaments and microtubules to form the net-like structure  
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Microtubules   long, relatively stiff hollow tubes; approximately 25nm; can be rapidly disassembled and reassembled; visible using EM or light microscopy; polar and highly dynamic i  
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Tubulin   monomer of microtubules; consists of one molecule or alpha and beta-?  
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Alba tubulin   negative charge  
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Beta tubulin   positive charge  
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Cylindrical microtubule   25nm in diameter; thirteen columns of tubulin polymer  
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Assembly and disassembly of the microtubule   similar to the assembly of actin filaments; there is positive and negative end; GTP bound monomers (alpha-tubulin) assemble onto microtubule; GDP bound beta-tubulin monomers dissociate rapidly  
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Microtubules are polymerised in   centrosomes; minus end remains close the centrosome and the plus end points outward towards the cell periphery  
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Cell shape and orientation   actin filament bundles provide support; dense sheets of actin found in the cortex of cells; maintains the shape of cells e.g. erythrocytes (RBC);  
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Microvilli   Actin filament bundles provide for absorption in the gut byt forming an adhesion belt  
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Stereocilia   contains actin filaments; detect vibration in the cochlea; cells are depolarised or hyperpolarised by deflections caused by sound; actin filaments keep them rigid  
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Shape of axons   intermediate filaments and microfilaments support shape  
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Stabilise the shape of plates   microfilaments provide support; protrusions are activated by cuts and formed by microfilaments allowing them to adhere to one another and form a clot  
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Form meshwork around the cell nucleus hold it into position   Intermediary filaments  
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Hold synaptic vesicles close to the presynaptic membrane   actin filaments  
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Organise the ER of a cell   microtubules  
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Anchoring cells   cytoskeleton is essential; to extracellular matrix at cell junctions and to each other  
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Actin-based movement   cell motility; e.g.migration of neutrophils (WBC) to sites of infection for phagocytosis F  
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Event 1 of actin-based movement   cell pushes out protrusions at the front (leading edge); actin filament polymerisation provides to force of membrane protrusion  
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Event 2 of actin-based movement   protrusions adhere to the surface on which the cell is moving through contact junctions; F-actin connects to the focal adhesions to provide a contractile force for the cell  
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Event 3 of actin-based movement   the rest of the cell pulls against the anchorage points to drag itself forward  
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Event 4 of actin-based movement   actin depolymerises at the rear  
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Lamellipodia   is a cytoskeletal protein actin projection on the leading edge of the cell; sample the environment; extend and withdraw; generated by rapid growth of actin filaments at the cell membrane; the (+) end of actin filaments are oriented towards the periphery  
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Lamellipodia or filopdia touch down   they attach to the extracellular matrix through the formation of focal adhesions (focal contacts); actin filaments connect the focal adhesion to the rest of the cytoskeleton  
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Myosin   motor protein; pull on actin filaments to drag the cell forward; specially myosin II filaments; doesn't stay bound to actin all the time (unusual)  
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Myosin "head region"   interacts with actin and binds ATP; energy release from ATP hydrolysis forces the myosin tail to move, generating force;  
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Myosin head movement   ADP is released from the myosin head and replaced by ATP at which stage the head can detach from the actin filament; the head binds further down the filament  
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Microtubule based movement   cilia and flagella; microtubules slide along one another causing the cilium to bend  
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Dynein   a minus-ended microtubule associated motor protein;  
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Kinesin and dynein   involved in the movement of organelles, e.g. synaptic vesicles along axons to synapses; composed of heavy chain (binds to microtubule) and light chain (binds to what needs to be moved)  
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Kinesin   moves towards (+) ends (cell periphery); stays attached to the microtubule throughout the ATP hydrolysis cycle (unlike mysosin)  
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Dynein   moves toward (-) ends (near nucleus)  
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Vesicles move   10cm/day which take more than a week down an entire axon  
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Processive motor protein   e.g. kinesin and dynein; capable of moving great distances along microtubules; stays bound to the microtubule  
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Non-processive motor protein   e.g. myosin II; detaches completely from actin filaments at the end of the cycle; will travel only short distances; constantly bound and un-bound depending on hydrolysis of ATP  
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Involves in separation of chromosomes during cell division (interphase, metaphase, telophase)   microtubules  
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Colchicine, vinblastine and taxol   anti-cancer therapeutics; inhibit the function of the mitotic spindle and thus cell division  
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Colchicine and vinblastine   destabilise microtubules; inhibits microtubule polymerization by binding to tubulin  
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Taxol   stabilises microtubules; also acts on tubulin  
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Dystrophin   rod-shaped cytoplasmic protein, and a vital part of a protein complex that connects the cytoskeleton of a muscle fiber to the surrounding extracellular matrix through the cell membrane; mutations causes Duchenne and Becker Muscular Dystrophy  
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Myosin VII mutations   causes Usher's Syndrome; hereditary deafness and blindness  
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Epidermolysis bullosa symplex   disease of the intermediate filaments; mutations in keratin genes results in failure to form proper keratin filaments in epidermis; skin highly sensitive to mechanical energy; blistering in adults and sloughing of epidermis in newborns  
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Epidermolysis bullosa symplex (EBS) and muscular dystrophy   disease of the intermediate filaments caused my plectin mutations  
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Amyotrophic lateral sclerosis (ALS) or Motor Neuron disease   some hereditary forms are caused by mutations in neurofilamin genes  
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Microtubules   alongside amyloid plaques, AD brains display neurofibrillary tangles comprising MAP, Tau  
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Tau   hyperphosphorylated in tangles and cannot bind microtubules  
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Hereditary Spastic Paraplegia   most commonly caused by mutations in spastin  
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Spastin   microtubule severing protein  
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Listeria bacteria   hijack actin of cytoskeleton; engulfed by host cell; escapes from phagocytic vesicle; F-actin is polymerised at the back of it, providing motility; actin "comet" drives it into the neighbouring cell  
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Listeriosis   causes infections of the central nervous system (meningitis, meningoencephalitis, brain abscess, cerebritis) and bacteremia in those who are immunocompromised; from eating contaminated foods  
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