PowerPoint PresentationSlide 2Slide 3Slide 4Slide 5Slide 6Slide 7Slide 8Slide 9Slide 10Slide 11Slide 12Slide 13Slide 14Slide 15Slide 16Slide 17Slide 18Slide 19The Cell Cytoskeleton 1The Cell Cytoskeleton Chapter 17Questions in this chapter you should be able to answer:Chapter 17: 1 - 11, 13 - 23Watch this animationhttp://multimedia.mcb.harvard.edu/ anim_innerlife.htmlThe Inner Life of CellsThe Cell Cytoskeleton 2The Cell CytoskeletonWhat are the 3 primary typesof cytoskeletal proteins?Intermediate filaments-- resist mechanical stressMicrotubules-- cytoplasmic transport-- axoneme movement -- chromosome movementActin filaments-- membrane contraction-- muscle cells-- cytokinesis-- cell movementsThe Cell Cytoskeleton 3What is the structure of intermediate filamentsCable-like arrangementExtended molecular interactionsAnchoring to desmosomesIntermediate FilamentsThe Cell Cytoskeleton 4Distribution and functions of IFs?Cytoplasmic -- keratins – skin integrity  -- in neurons -- in muscle, connective tidssueNuclear -- lamins-- progeria connection??The Cell Cytoskeleton 5What is the fundamental structure of microtubules?Alpha and beta tubulin subunits13 member ringWhy do MTs have polarity?‘MT Organizing Center’Why are MTs said to display ‘Dynamic Instability’? Dynamic InstabilityThe Cell Cytoskeleton 6What is the mechanism of MT growth and retraction?Binding, hydrolysis and release of GTP‘Capping’ at cell membraneQuestion 17-3, p 583How would a change in [tubulin] affect MT dynamics?..if only GDP were present?… or a nonhydrolizable GTP analog?MT with EB1 capThe Cell Cytoskeleton 7How do MTs facilitate cytoplasmic transport?Motor proteinskInesin & dyneinKinesin walkingOrganelle movementThe Cell Cytoskeleton 8What is the structure and movement of an axoneme?Cilia & flagella“9 + 2 Structure”Lining Cell videoThe Cell Cytoskeleton 9Axoneme mutations and Immotile Cilia SyndromeDiagnosisSymptoms; respiratory infection; situs inversus, flagella and embryonic development - IDA - ODA- IDA Morillas HN, Zariwala M, Knowles MR. 2007. Genetic Causes of Bronchiectasis: Primary Ciliary Dyskinesia. Respiration 2007;74:252-263The Cell Cytoskeleton 10What is the distribution and structure of actin filaments?treadmillingThe Cell Cytoskeleton 11How are actin filaments organized in the cytoplasm?The cell cortexActin binding proteinsThe Cell Cytoskeleton 12How does actin mediate cell movements?Cell crawlingWhat are Lamellipodia and Filopodia?Membrane rufflingListeria movementThe Cell Cytoskeleton 13Actin, myosin and muscle contractionSome basic anatomy. . .Muscle are bundles of muscle cellsMuscle cells contain myofibrilsSarcomere is contractile unit of myofibrilThe Cell Cytoskeleton 14How are actin and myosin arranged within a sarcomere?Structure of a myosin-II thick filamentMyosin motor proteins I & IIThe Cell Cytoskeleton 15How does myosin interact with actin filament?What happens to the sarcomere during contraction?The Cell Cytoskeleton 16Myosin is attached ATP binds -- Myosin head detachesATP is hydrolyzed -- Myosin Head cocks -- loosely binds to actinPi is released -- which triggers ….Powerstroke -- during which…ADP is releasedMyosin remains attachedHow does the sliding filament model explain sarcomere contraction?myosinThe Cell Cytoskeleton 17How is muscle contraction triggered?Motor neuron & action potentialSarcoplasmic reticulumT-tubulesCa++ releaseThe Cell Cytoskeleton 18How does Ca++ trigger the muscle contraction?The tropomyosin / troponin complexSarcomereThe Cell Cytoskeleton 19QuestionIn order to keep cytosolic Ca++ levels low, muscle cells possess an ATP driven Ca++ pump in the sarcoplasmic reticulum and a Ca++/Na+ ATPase in the cell membrane. The cells also possess the Na+/K+ ATPase in the cell membrane. The Na+/K+ ATPase is partially inhibited by drugs such as ouabain and digitalis, whereas the Ca++/Na+ ATPase is inhibited by binding to a protein called phospholamban.A. Draw a diagram showing the expected arrangement and orientation in the membranes of these membrane proteins.B. Would treating a patient with either of these drugs weaken or strengthen muscle contraction (they are usually given to cardiac patients)? Explain.C. The regulatory protein “protein kinase C” (PKC) regulates activity of the Ca++ ATPase. PKC can phosphorylate (covalently add a PO4) to the Ca++ ATPase, which increases its affinity for Ca++. What would be the expected effect of Ca++ ATPase phosphorylation on the strength of muscle