The Cell Cytoskeleton Chapter 17

1. The Cell Cytoskeleton Chapter 17 Watch this animation http://multimedia.mcb.harvard.edu/ anim_innerlife.html The Inner Life of Cells Questions in this chapter you should be able to answer: Chapter 17: 1 - 11, 13 - 23 The Cell Cytoskeleton

2. What is the Cell Cytoskeleton? -- long protein filaments -- extend through the cytoplasm A variety of purposes Three families • Microtubules • Actin filaments • Intermediate filaments The Cell Cytoskeleton

3. The Cell Cytoskeleton What are the 3 primary types of cytoskeletal proteins? Intermediate filaments -- resist mechanical stress Microtubules -- cytoplasmic transport -- axoneme movement -- chromosome movement Actin filaments -- membrane contraction -- muscle cells -- cytokinesis -- cell movements The Cell Cytoskeleton

4. What is the structure of intermediate filaments Cable-like arrangement Extended molecular interactions Anchoring to desmosomes Intermediate Filaments The Cell Cytoskeleton

5. Intermediate filaments -- help hold cells & tissues together Human lung carcinoma The Cell Cytoskeleton

6. Intermediate filaments also occur in the nucleus Cytoplasmic -- keratins – skin integrity  -- in neurons -- in muscle, connective tidssue Nuclear -- lamins The Cell Cytoskeleton

7. Microtubules & Actin filaments make possible different types of movements Cell migration Neutrophil Flagella and cilia Cytoplasmic movements Muscle contraction Mitosis and Cell division Cytoplasmic transport Membrane movements Membrane ruffling The Cell Cytoskeleton

8. Cytosolic Microtubules Helps to distribute materials through the cell This highway is ‘dynamic’ The Cell Cytoskeleton

9. Motor proteins carry “cargo” along microtubules Two motor proteins Opposite directions How does Kinesin ‘walk”? Organelle movement Kinesin walking The Cell Cytoskeleton

10. What is the fundamental structure of microtubules? Alpha and beta tubulin subunits 13 member ring Why do MTs have polarity? ‘MT Organizing Center’ Why are MTs said to display ‘Dynamic Instability’? Dynamic Instability The Cell Cytoskeleton

11. What is the mechanism of MT growth and retraction? Binding, hydrolysis and release of GTP ‘Capping’ at cell membrane MT with EB1 cap Question 17-3, p 583 How would a change in [tubulin] affect MT dynamics? ..if only GDP were present? … or a nonhydrolizable GTP analog? The Cell Cytoskeleton

12. The ‘spindle apparatus’ controls chromosome movements -- Attached to “kinetochores” on duplicated chromosome Spindle Apparatus The Cell Cytoskeleton

13. What is the structure and movement of an axoneme? Cilia & flagella “9 + 2 Structure” Living Cell video The Cell Cytoskeleton

14. Where are human cilia and flagella found? Various places Some genetic conditions cause cilia not to function Respiratory cilia The Cell Cytoskeleton

15. An interesting congenital genetic disorder -- “Immotile Cilia Syndrome” Symptoms: • Respiratory tract infections • Infertility • Digestive problems • Situs Inversus -- Affects ~50% of people with IMS - IDA - ODA - IDA The Cell Cytoskeleton

16. What is the link between cilia and Left/Right orientation? Cilia occur in the “embryonic node” -- very early stage of development Generate oriented flow of signal molecule Why 50% affected? Embryonic node cilia The Cell Cytoskeleton

17. What is the distribution and structure of actin filaments? treadmilling The Cell Cytoskeleton

18. How are actin filaments organized in the cytoplasm? The cell cortex Actin binding proteins The Cell Cytoskeleton

19. How does actin mediate cell movements? Cell crawling What are Lamellipodia and Filopodia? Membrane ruffling Listeria movement The Cell Cytoskeleton

20. Actin, myosin and muscle contraction Some basic anatomy. . . Muscle are bundles of muscle cells Muscle cells contain myofibrils Sarcomereis contractile unit of myofibril The Cell Cytoskeleton

21. Sarcomeres create visual ‘striations ‘of “Striated muscles” (skeletal muscles) The Cell Cytoskeleton

22. Some details of Sarcomeres, Actin and Myosin… α-actin filaments Myosin-I “thick milaments The Cell Cytoskeleton

23. How does the sliding filament model explain sarcomere contraction? Myosin is attached ATP binds -- Myosin head detaches ATP is hydrolyzed -- Myosin Head cocks -- loosely binds to actin Pi is released -- which triggers …. Powerstroke -- during which… ADP is released Myosin remains attached myosin The Cell Cytoskeleton

24. Muscle spasms and cramps (“Charley Horse”) Imbalance in excitatory and inhibitory signals -- self-reinforcing cycle occurs The Cell Cytoskeleton

25. How does action potential trigger muscle contraction? Motor neuron & action potential Sarcoplasmic reticulum T-tubules Ca++ release The Cell Cytoskeleton

26. How does Ca++ trigger the sarcomere contraction? The tropomyosin / troponin complex Sarcomere The Cell Cytoskeleton

27. Question After the voltage-gated Ca++ channel releases Ca++ from the sarcoplasmic reticulum to trigger a sarcomere contraction, two channels act to quickly remove the Ca++ from the cytosol: 1) an ATP driven Ca++ pump in the sarcoplasmic reticulum, and 2) a Ca++/Na+ antiport in the cell membrane. The cells also possess the Na+/K+ ATPase in the cell membrane.. A. Draw a diagram showing the expected arrangement and orientation in the membranes of these membrane proteins. B. A protein called “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 contraction? Explain C. The Na+/K+ ATPase is partially inhibited by drugs such as ouabain and digitalis. Would treating a patient with either of these drugs weaken or strengthen muscle contraction (they are usually given to cardiac patients)? Explain. The Cell Cytoskeleton