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Medical Cell Biology

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