Cytoskeleton - Chapter 17 - April 24 3rd Exam PDF

Chapter 17 Cytoskeleton April 19 (F)- April 22 (M) and April 26 (F) April 24- 3rd exam Composition:  protein filaments fibrous  tubulin dimers globular  actin monomers globular Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company Intermediate Filaments provides tensile st...

Chapter 17 Cytoskeleton April 19 (F)- April 22 (M) and April 26 (F) April 24- 3rd exam Composition:  protein filaments fibrous  tubulin dimers globular  actin monomers globular Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company Intermediate Filaments provides tensile strength; resist mechanical stress most durable among the cytoskeletal filaments – not defined by composition but by it’s diameter’s size protects Cell Skin an Form a strong, durable network in the cytoplasm our from stress cell is example the for structure intermediate the accounts Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company Structure: without polarity DNA S'phosphate / hidroxy Polarity to e Lecture known are They e tetramers can pack together end- to-end and assemble in a helical array containing 8 strands of tetramers that generates the final ropelike intermediate filament Intermediate Filaments: Where are they found? Intermediate filaments support and strengthen the nuclear envelope. (A) The intermediate filaments of the nuclear lamina line the inner face of the nuclear envelope and are thought to provide attachment sites for the chromosomes. (B) Electron micrograph of a portion of the nuclear lamina from a frog egg. The Nuclear Envelope Is Supported by a Meshwork of Intermediate Filaments  the nuclear lamina disassemble & reform at each cell division  when the lamins are phosphorylated it weakens The Centrosome Is the Major Microtubuleorganizing Center in Animal Cells Microtubules grow out from the small structure near the center of the cell called the centrosome. Centre some grow metaphase Chromosomes act O ne in pulledopposite directions basal body Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company would motor protein dunein - be movement Sweeping movement Waves for movement Have Flagella ↓ microtobules Figure 17-24 Essential Cell Biology (© Garland Science 2010) is motor proteinL called dynein microtubes > and motor protein Many hairlike cilia project from the surface of the epithelial cells that line the human respiratory tract. - Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company Flagella propel a cell through fluid using repetitive wavelike motion. Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company Cilia and Flagella Contain Stable Microtubules Moved by Dynein defects in dynein causes Kartagener’s syndrome makes infertility are the because cannot Sperm move, they respiratory also have infection all the time becausethet absence Figure 17-27 Essential Cell Biology (© Garland Science 2010) of move dunein Kartagener’s syndrome In humans, hereditary defects in dynein cause Kartagener’s syndrome– where afflicted men are infertile because their sperm are immotile, and they do have an increased susceptibility to bronchial infection. Pomer is < MICROTUBULES ARE HOLLOW TUBES WITH STRUCTURALLY DISTINCT ENDS gives directionality has polarity – gives directionality They are built from sub-units called tubulin dimers. B a Figure 17-11 Essential Cell Biology (© Garland Science 2014) Tubulin polymerizes from nucleation sites on a centrosome. Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company Microtubules can be stabilized by attachment to capping proteins. Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company Intermediate filaments: stable: Microtubules: Dynamic Instability Actin Filament: Threadmilling GTP hydrolysis controls the dynamic instability of microtubules. Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company  If microtubule growth is slow, the dimers in this GTP cap will hydrolyze their GTP to GDP before fresh dimers loaded with GTP have time to bind.  The GTP cap is thereby lost. Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company MICROTUBULE DYNAMICS CAN BE MODIFIED BY DRUGS Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company Clinical Correlation Anti-mitotic drugs; anti-cancer drugs COLCHICINE- binds tightly to free tubulin and therefore prevents microtubule polymerization Effect: arrest of cell division Clinical Correlation Anti-mitotic drugs; anti-cancer drugs TAXOL- binds tightly to microtubules and prevents them from losing subunits (prevents shrinking) Effect: it also arrest arrests dividing cells in mitosis Cancer cells which are dividing with less control can be killed by microtubule-stabilizing and microtubuledestabilizing antimitotic drugs. Microtubules help position organelles in a eukaryotic cell. Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company Microtubules Organize the Interior of the Cell The ER is being pulled towards the membrane by the MOTOR proteins. Figure 17-18 Essential Cell Biology (© Garland Science 2010) On the other hand, the Golgi is being pulled away from the membrane by the MOTOR proteins. Microtubules allow transport of cell components. Organelles Move Along Microtubules organelle_movement.wmv Microtubules work with other proteins to do its work. Motor Proteins Drive Intracellular Transport On the other hand, myosin is another motor protein. It is involve in contraction. Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company o ATP hydrolysis and phosphate release by the rear motor head loosens its attachment to the microtubule. o ADP release and ATP binding by the front motor head then cause a dramatic conformational change that flips the rear motor head to the front, thereby completing a single step. Conformational changes result in motor proteins movement ATP is bound and hydrolyzed Different motor proteins transport different types of cargo along microtubules. Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company MICROTUBULES Microtubules Are Hollow Tubes with Structurally Distinct Ends The Centrosome Is the Major Microtubule-organizing Center in Animal Cells Microtubules Display Dynamic Instability Dynamic Instability Is Driven by GTP Hydrolysis Microtubule Dynamics Can Be Modified by Drugs MICROTUBULES Microtubules Organize the Cell Interior Motor Proteins Drive Intracellular Transport Microtubules and Motor Proteins Position Organelles in the Cytoplasm Cilia and Flagella Contain Stable Microtubules Moved by Dynein ACTIN FILAMENTS Essential for cell movements Key to changing cell shape – Structures formed depend on actin filaments association with different proteins Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company Many Proteins Bind to Actin and Modify Its Properties Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company Actin Filaments Are Thin and Flexible growth is by addition of actin monomers Actin and Tubulin Polymerize by Similar Mechanisms actin monomer with ATP to ADP binding reduces binding between monomers and thus decreases stability of polymer actin monomer with ATP to ADP binding reduces binding between monomers and thus decreases stability of polymer Supplementary video: https://www.youtube.com/watch?v=Z5q0-jnKHqM Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company Actin filaments can undergo treadmilling. When the rates of addition and loss are equal, the filament stays the same length— Actin-specific Drugs Action Phalloidin Binds and stabilizes filaments Cytochalasin Caps filament plus ends, preventing polymerization there Binds actin monomers and prevents their polymerization Latrunculin Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company ACTIN FILAMENTS Actin Filaments Are Thin and Flexible Actin and Tubulin Polymerize by Similar Mechanisms Many Proteins Bind to Actin and Modify Its Properties A Cortex Rich in Actin Filaments Underlies the Plasma Membrane of Most Eukaryotic Cells Actin filaments allow animal cells to migrate. Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company Filipodium versus Lamellipodium Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company Cell Crawling Depends on Actin Cell Crawling Depends on Actin What are the four steps of cell crawling? Cell Crawling Depends on Actin 1. Extension 2. Adhesion 3. Translocation (Contraction) 4. De-adhesion (Cell Body Moves Forward) Force generated in the actin-rich cortex move a cell forward 1. The cell pushes out protrusions 2. The protrusions adhere to the surface over which the cell is crawling 3. Cell drags itself forward by traction on these anchorage lamellipodium Figure 17-33a, b Essential Cell Biology (© Garland Science 2010) filopodium Nucleation of new actin filaments forming lamellipodia is mediated by ARP (actin related proteins) Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company Nucleation of new acting filaments forming fillipodia is mediated by formin. Extracellular Signals Control the Arrangement of Actin Filaments Activation of the receptor proteins, signal transduce to monomeric GTP binding proteins called Rho protein family Activation of Rho-family GTPases can have a dramatic effect on the organization of actin filaments in fibroblasts. bundles sheets lamellipodia formation extensions filipodia formation Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company Actin associates with myosin to form contractile structures Actin dependent motor proteins belong to the myosin family Myosin I and myosin II are the most abundant one head and a tail Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company Learning Outcomes Describe the structures- - muscle cell, myofibrils, sarcomere Describe muscle contraction Explain- - How muscle contraction is triggered by sudden rise in Ca2+ Muscle Contraction Muscle Contraction Depends on Bundles of Actin and Myosin During Muscle Contraction Actin Filaments Slide Against Myosin Filaments Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company Muscle contraction depends on interaction of actin and myosin II. o Has two ATPase heads and a tail, dimer o Clusters of myosin II molecules bind to each other through their tails o Clusters of myosin II: heads project on both sides Muscle Contraction Depends on Bundles of Actin and Myosin Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company A skeletal muscle is packed with myofibrils o Skeletal muscle are huge single cells formed by fusion of many separate smaller cells. o The bulk of cytoplasm is made up of myofibrils. o contractile elements of the muscle cells What is a sarcomere? Describe contraction. o Each myofibril is made up of sarcomeres. o Sarcomeres are assemblies of actin filaments and filaments of myosin II. Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company Sarcomere contractile unit Z-disc consists of actin filaments coming from adjacent sarcomeres which are crosslinked by αactinin molecules. Z-disc consists of actin filaments coming from adjacent sarcomeres which are crosslinked by α-actinin molecules. Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company Muscles contract by a sliding filament mechanism. o during contraction the actin and myosin slide past each other without shortening. o sliding motion driven by the myosin heads walking toward the plus end of the adjacent actin filament the filaments themselves remain the same length, the sarcomere to which they belong shortens without calcium Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company with calcium Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company Muscles contract by a sliding filament mechanism without calcium with calcium http://www.youtube.com/watch?v=CepeYFvqmk4 (on hyperlink, click while on slideshow)  Discuss how a myosin molecule walks along an actin filament through a cycle of structural changes  Using actin and myosin discuss how chemical energy is converted to mechanical energy CLASS: 9:37 http://www.youtube.com/watch?v=zopoN2i7ALQ weak binding of the myosin causes released of Pi this release triggers a power stroke –the force generating change in shape in which the head retains its original conformation o a large shape change that causes the head to be displaced along the filament by a distance of 5 nm o ATP hydrolysis http://www.youtube.com/ watch?v=zopoN2i7ALQ Recall: Think about the following: Neurotransmitters: Acetylcholine Ligand-Gated Ion Channel Action Potential  How a muscle contraction is signaled?  How does sudden rise in Ca2+ trigger muscle contraction? Signal received from a nerve terminal triggers an action potential. Action Potential Sarcoplasmic Reticulum Voltage-sensitive protein T-tubules Calcium Channel rush of calcium from the lumen of SR to the cytosol T tubules and the sarcoplasmic reticulum surround each myofibril. Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company Muscle contraction is triggered by sudden rise in Ca2+ Signal received from a nerve terminal triggers an action potential. Electrical excitation spreads into a series of membranous tubes – transverse tubes Muscle contraction is triggered by sudden rise in Ca2+ Electrical signal relayed to the sarcoplasmic reticulum - flattened vesicles; specialized region of the ER in the muscle cells Muscle contraction is triggered by sudden rise in Ca2+ Ca2+ channel Ca2+ release channel in sarcoplasmic reticulum membrane is thought to be opened by a voltage sensitive transmembrane protein in the adjacent T tubule. Skeletal muscle contraction is controlled by tropomyosin and troponin complexes. Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company Ca2+ binding to the troponin complex (not shown in the next figure) leads to movement of tropomyosin away from the myosin-binding site Then myosin binds and walks along the actin filament allowing Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company  Discuss how a myosin molecule walks along an actin filament through a cycle of structural changes  Using actin and myosin discuss how chemical energy is converted to mechanical energy Skeletal Muscle Contraction Is Controlled By Troponin When Ca2+ binds to troponin, the troponin moves the tropomyosin that blocks the interaction of actin with myosin heads How does sudden rise in Ca2+ trigger muscle contraction? Action potential traverses T-tubules How does sudden rise in Ca2+ trigger muscle contraction? Muscles contract by a sliding filament mechanism Without Calcium With Calcium In non skeletal muscle cells…. non muscle cells, smooth muscle cells (e.g. walls of stomach, uterus, arteries) Myosin II also activated by rise in Ca 2+ Mechanism: increase in calcium leads to phosphorylation of myosin II, enabling it to interact with actin filament Muscle Contraction Actin Filaments Slide Against Myosin Filaments During Muscle Contraction Muscle Contraction Is Triggered by a Sudden Rise in Cytosolic Ca2+ Different Types of Muscle Cells Perform Different Functions – heart or cardiac muscle- drives circulation of the blood – smooth muscle- maintenance of organ dimensions Summary Cytoplasm supported by cytoskeleton filaments – Intermediate filaments- provides tensile strength – Microtubules – organelle organization and movement – Actin – cell movement Motor Proteins – dynein and kinesin with microtubules – myosin with actin Summary Growing microtubules (as well as actin polymer) show dynamic instability- controlled by dNTP hydrolysis Overlapping actin filaments and myosin filaments generate contractions by sliding over one another – rise in cytosolic Ca2+ delivers signal to contractile apparatus via Ca2+ binding proteins