Medical Cell Biology
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| Functions of Cytoskeleton | Provides structural integrity, cell motility/contraction of muscles, change in cell shape, and movement of organelles
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| 3 Types of Muscle | skeletal, cardiac, and smooth
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| Skeletal Muscle | striated, multi-nucleated, consist of actin and myosin
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| Sacromere | Functional contractile unit of a skeletal muscle
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| 3 Layers of connective tissues surround skeletal muscle | Epimysium, Perimysium, and Endomysium
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| Epimysium | Surround the whole muscle (group of muscle fasciculi)
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| Perimysium | Surround muscle fasciculous (bundle of muscle fibers)
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| Endomysium | Surround individual muscle fiber.
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| Z Disk | actin thin filaments
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| A band | Remain constant during contraction
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| I Band | Shortens during contraction
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| H Band | Center of A band, overlapping of thick and thin filament (thick filament)
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| M Line | Anchor thick filament (myosin)
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| Actin | composed of F-actin (polymerize) and G actin (globular protein)
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| What is important about the G-protein? | Binds to ATP to polymerize F-actin. Polymerization: need ATP and Mg2+
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| Tropomyosin | Wrap around the thin filament
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| Troponin | Bind to tropomyosin (block the myosin head binding site) TnC, TnI, TnT
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| Tropomodulin | Cap slow growing end (-)
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| Polymerization of actin | Lag phase, polymerization phase, and Steady Phase,
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| Steady Phase | Also known as tread milling Effect. Monomers added is equal to the number of monomers removed. Addition of G-actin ATP (+ end) = loss of G-actin ADP (-end)
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| Tropomyosin | Wrap around the thin filaments for stability of F-actin
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| Z disk proteins | Cap Z and alpha actinin (anchored thin filament)
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| Cap Z | bind to + end of F-actin prevent growth and depolymerization
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| Alpha actinin | Space b/w thin filaments so thick filaments won't bind
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| Titin | Keep myosin thick filament centered
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| Nebulin | extended from Z-disk to (-) end of thin filament
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| Desmin | Stabilize the Z-disk
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| Myosin | consists of 2 heavy chains and 2 light chains. Formed in coiled-coil helix fashion with a repeat sequence of amino acids- to avoid aqueous solution
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| Papain | Cleave myosin heads
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| Rigor Mortis | Occurs when there is no ATP. The myosin head remain binding to the actin filament - Stiffness
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| Calcium regulation | Troponin complex bound to tropomyosin, block the binding site for myosin head.
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| What happens when Ca binds to Troponin C? | Moves troponin away from the tropomyosin. This exposes actin to the myosin head
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| Sarcroplasmic Reticulum | Stores Ca++, consists of 2 terminal cisternae and one T-tubule (triad)
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| DHPR (Dihydropyridine receptor) | Locates along the T-Tubule, which will undergoe a conformational change.
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| Ryanodine receptor | Ca2+ channel of the SR. This SR Ca2+ channel open and release Ca2+ into the cytosol
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| Calsequestrin | Takes back Ca into the SR by Ca2 ATPase
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| Cardiac Muscle Cell | Location of the nuclei is in the center where as the location of the nuclei in a skeletal muscle is in the periphery. Contraction is the same as skeletal muscle
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| Intercalated disks | Only present in Cardiac cells
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| Gap Junctions | Located in intercalated disks. It is for synchronizing the contraction (allow rapid exchange of solutes and ions)
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| Desmosome (macula adherens) | Hold cells together
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| Fascia adherens | Hold actin thin filament together like Z-disk
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| Familial Hypertrophy Cardiomyopathy | Defect in cardiac B-myosin
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| Familial Dilated Cardiomyopathy | Defect in cardia a-actin
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| Smooth Muscles | No sarcomere, no troponin, not striated. Has dense bodies, lots of IFs (desmin, vimentin). Ratio of thin to thick 12:1. Made up of Dense bodies
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| Dense Bodies | Made up of a-actinin
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| Myosin Light Chain Kinase | Phosphorylates Myosin Light chain
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| Ca2+ Calmodulin - Contraction | Myosin light chain kinase is inactive when Ca-calmodulin complex form. This will phosphorylate myosin light chain and become active
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| Ca2+ Calmodulin - Relaxation | Dephosphorylation of myosin light chain by removing pi by phosphatase
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| Catcholamine | Binds to Beta adrenergic receptors. Cause an increase in cAMP, which phosphorylates protein Kinase A
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| Protein Kinase A | Phosphorylates myosin light chain kinase - cause inability to bind to calmoduline-- lead to relaxation
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| Dephosphorylation of MLCK | Causes muscle to contract by dephosphorylation of MLCK. MLCK is active
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| release of Ca+2 and DAG is stimulated by which kinase? | Protein kinase C
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| Caldesmon | Ca+2 proteins that interact with actin thin filaments
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| Contractile Ring | Present during telophase of mitosis. During mitosis, actin filaments form at cleavage site-cleavage furrow. Myosin polymerises with actin contractile ring
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| Villin and fimbrin | Bundled together and then attach to microvilli. Increase surface area for absorption at + end
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| Spectrin II and Myosin II | Link two bundles together at terminal web. Microvilli anchored at terminal web.
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| Gelsolin | Keep cytosol liquification that is triggered by increased calcium. Makes fragment filaments
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| Profilin | Polymerization. When PIP2 is bound to profilin, profilin cannot bind to actin. When PIP2 hydrolyzes to IP3 and DAG by PLP-C release profilin
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| Thymosin | Binds to G-actin and keep it in that state
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| Cytochlasin | Inhibitors of actin filament. Blocks plus end
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| Paballoidin | Stabilize microfilament does not allow depolarization
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| Protrusion | Actin polymerization. If polymerization is greater than retrograde flow = cell protrusion
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| Retrograde flow | myosin II contractile
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| Arp 2/3 nucleating complex | Branching of lamellipodia
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| Lamellipodia and filopodia | extension at leading edge for cell movement
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| WasP and Scar | Binds to Arp 2/3 - promote actin polymerization
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| Cdc42 | Activate Scar bind to Arp 2/3 form filopodia
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| Rac | Activate Wasp and PI (4) P5 kinase form lamellipodia and membrane ruffles
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| Rho | Bundling of actin with myosin II.
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| Rhokinase | Phosphorylates myosin II--contracation
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| ERM proteins | Ezrin, Radixin, Moesin
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| Defect Merlin | Leads to Neurofibromatosis
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| What attaches actin filament to plasma membrane | ERM Proteins
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| Spectrin 4.1 | Maintains biconcave shape of RBC
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| Ankyrin | Anchored spectrin to membrane. The whole complex is stabilized by protein 4.1
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| Ubiquination | Is needed for shaping RBC
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| Dystrophin | Protein that belong to spectrin gene family. If absent - responsible for Duchenne's Muscular Dystrophy
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| Intermediate filaments | Resistance to mechanical stress. (ankyrin and spectrin II)
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| Keratin filament | Epithelial Cells
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| Neurofilament | Neurons
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| Vimentin | Containing filaments - fibroblasts/glial cells/ muscle cells
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| Nuclear Lamina | All nucleated cell (except RBC)
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| GFAP | brains
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| Microtubules | Need tubulin alpha and beta. 13 protofilament. Flagella and cilia motility, Meitotic and mitotic spindles. Vesicle transport. Need GTP
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| Drugs that Target Microtubules | Colchine, Viblastine sulphate, Nocodazole, Paclitaxel
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| Polarity | addition of subunit is faster at (+) end, (-) end is capped due to centrosome complex
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| Centrosome complex | Composed at 9 short-triplet microtubules (9+2 arrangement)
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| Kinesin | Anterograde transport (-end to +end)
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| Dynein and KRPS | Retrograde transport + end to - end
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| Dynactin Complex | Arp 1, Spectrin, Dynein
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| APP (Amyloid Precursor Protein) | Defect in MAMR (membrane associated motor receptors causes Alzheimer's disease
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| Dynein | ATPase extending towards B Tubule
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| Nexin | Attaches neighboring doublets
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| Radial Spokes | Attach doublets to the center
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| Arrangement of Microtbules in cilia and flagella | Arranged in 9+2 array. Doublet alpha tubule and beta tubule
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| Metaphase | Chromosome line in the middle - 2 forms: interpolar (overla of the spindles) and ASTRAL (GROWING AWAY FROM THE KINETOCHORE)
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| Telophase | Cytokinesis (contractile ring) - form daughter cell membrane
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| MAPs and Tau | Bind to tubulin monomoer of microtubule-allow bundling and stabilize MT
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| MAPs (EB 1 and CLIP 170) | Attach MT to kinetochore
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| Katanins and Stathmins/Op18 | Disrupt microtubules formation
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| Katanins | Prevent the additions of tubulins to MTs by binding to tubulins dimer
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| Stathmin | Detach MTs from MTOC
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