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The Cytoskeleton
Biochemistry, Medicine, Phase 1
| Term | Definition |
|---|---|
| Cytoskeleton | a network of protein filaments that extend throughout the cell |
| The cytoskeleton determines | cell shape and polarity; tissue structure; adhesion; cell movement; intracellular movement (of vesicles and of chromosomes) |
| Three classes of protein polymer (or filament) | actin, intermediate filaments, microtubules |
| Actin | microfilaments; composed of actin-binding proteins; comprises 5% total protein |
| Microtubules | composed of micro-tubule-associated proteins (MAPs) |
| Actin filaments (1) | called F-actin (filamentous actin or microfilaments); are polymers of individual actin proteins called G-actin (globular actin) |
| Actin monomers | G-actin (globular actin) |
| Actin filament (2) | polarised double helix; 13 actin subunits for every complete turn |
| Diameter of actin filament | 7nm |
| 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 |
| G-actin adds more rapidly to | (+) end of the filament; once incorporated, ATP is hydrolysed to ADP |
| G-actin is removed more rapidly from | (-) end of the filament |
| 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 |
| Cell migration | happens a lot during embryogenesis but also adulthood; also pathogensis (metastasis); actin filaments turn over rapidly |
| Major function | mechanical support; cell shape changes and maintenance; cell motility |
| Actin-binding proteins | modulate polymerisation dynamics and function; |
| Membrane-attachment proteins | spectrin; bind to G-actin |
| Severing proteins | geisolin, severin; bind to F-actin |
| Cross-linkingproteins | transgelin; bind to F-actin |
| Capping proteins | prevent filament grown; bind to F-actin |
| Actin-sequestering proteins | bind to G-actin and prevent its polymerising; |
| Actin-bundling protein | alpha-actinin in muscle |
| Motor proteins | myosin in muscle; bind to F-actin |
| Side-binding proteins | interaction with other proteins; bind to F-actin |
| Intermediate filaments | polymer of individual intermediate filament proteins; 10nm in diameter; visible by electro microscope; not dynamic |
| Intermediate filament network | typically more dense around the nucleus; can extend into the periphery |
| 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) |
| Intermediate filament names by cell type | keratin, vimentin, glial fibriallary acidic protein, neurofilamin |
| Mice lack neurofilaments (NF+/-) | reduces axon diameter |
| 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 |
| Tetramer | fundamental unit of the intermediary filament; formed from two helical dimers |
| Growth of an intermediate filament | slow, not dynamic; subunit exchange occurs throughout the length of the filament |
| 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 |
| 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 |
| Tubulin | monomer of microtubules; consists of one molecule or alpha and beta-? |
| Alba tubulin | negative charge |
| Beta tubulin | positive charge |
| Cylindrical microtubule | 25nm in diameter; thirteen columns of tubulin polymer |
| 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 |
| Microtubules are polymerised in | centrosomes; minus end remains close the centrosome and the plus end points outward towards the cell periphery |
| 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); |
| Microvilli | Actin filament bundles provide for absorption in the gut byt forming an adhesion belt |
| Stereocilia | contains actin filaments; detect vibration in the cochlea; cells are depolarised or hyperpolarised by deflections caused by sound; actin filaments keep them rigid |
| Shape of axons | intermediate filaments and microfilaments support shape |
| 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 |
| Form meshwork around the cell nucleus hold it into position | Intermediary filaments |
| Hold synaptic vesicles close to the presynaptic membrane | actin filaments |
| Organise the ER of a cell | microtubules |
| Anchoring cells | cytoskeleton is essential; to extracellular matrix at cell junctions and to each other |
| Actin-based movement | cell motility; e.g.migration of neutrophils (WBC) to sites of infection for phagocytosis F |
| Event 1 of actin-based movement | cell pushes out protrusions at the front (leading edge); actin filament polymerisation provides to force of membrane protrusion |
| 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 |
| Event 3 of actin-based movement | the rest of the cell pulls against the anchorage points to drag itself forward |
| Event 4 of actin-based movement | actin depolymerises at the rear |
| 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 |
| 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 |
| 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) |
| Myosin "head region" | interacts with actin and binds ATP; energy release from ATP hydrolysis forces the myosin tail to move, generating force; |
| 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 |
| Microtubule based movement | cilia and flagella; microtubules slide along one another causing the cilium to bend |
| Dynein | a minus-ended microtubule associated motor protein; |
| 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) |
| Kinesin | moves towards (+) ends (cell periphery); stays attached to the microtubule throughout the ATP hydrolysis cycle (unlike mysosin) |
| Dynein | moves toward (-) ends (near nucleus) |
| Vesicles move | 10cm/day which take more than a week down an entire axon |
| Processive motor protein | e.g. kinesin and dynein; capable of moving great distances along microtubules; stays bound to the microtubule |
| 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 |
| Involves in separation of chromosomes during cell division (interphase, metaphase, telophase) | microtubules |
| Colchicine, vinblastine and taxol | anti-cancer therapeutics; inhibit the function of the mitotic spindle and thus cell division |
| Colchicine and vinblastine | destabilise microtubules; inhibits microtubule polymerization by binding to tubulin |
| Taxol | stabilises microtubules; also acts on tubulin |
| 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 |
| Myosin VII mutations | causes Usher's Syndrome; hereditary deafness and blindness |
| 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 |
| Epidermolysis bullosa symplex (EBS) and muscular dystrophy | disease of the intermediate filaments caused my plectin mutations |
| Amyotrophic lateral sclerosis (ALS) or Motor Neuron disease | some hereditary forms are caused by mutations in neurofilamin genes |
| Microtubules | alongside amyloid plaques, AD brains display neurofibrillary tangles comprising MAP, Tau |
| Tau | hyperphosphorylated in tangles and cannot bind microtubules |
| Hereditary Spastic Paraplegia | most commonly caused by mutations in spastin |
| Spastin | microtubule severing protein |
| 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 |
| Listeriosis | causes infections of the central nervous system (meningitis, meningoencephalitis, brain abscess, cerebritis) and bacteremia in those who are immunocompromised; from eating contaminated foods |
Created by:
emmaallde
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