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Regulation of Cytoskeletal Filaments

Regulation of Cytoskeletal Filaments

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Regulation of Cytoskeletal Filaments

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  1. Regulation of Cytoskeletal Filaments Pages 992-1010

  2. Most cytoskeletal regulation is performed by accessory proteins that bind to either the filaments of their free subunits. Microtubule-organizing center (MTOC) – a specific intracellular location where microtubule nucleation occurs

  3. Nucleation of Microtubules by gamma-tubulin - end + end

  4. The Centrosome, a MTOC 50 gamma-TuRC

  5. Cross-section of a Centrosome The centrioles organize the centrosome matrix ensuring its duplication during each cell cycle Centrioles are composed of a short cylinder of modified microtubules and a large number of accessory proteins Neither fungi nor most plants have centrioles Centriole

  6. Center-Seeking Behavior of a Centrosome

  7. Reorganization of Microtubules

  8. Nucleation by the ARP Complex ARP – actin-related protein, each ARP is about 45% identical to actin

  9. Structures of Actin, Arp2, and Arp3

  10. Actin Web Formation

  11. Binding of Profilin and Thymosin About 50% of actin in nonmuscle cells is in filaments and 50% as soluble monomers

  12. Profin bound to Actin Monomer - Profilin binds to the opposite side of the ATP-binding site, blocking the side of the monomer that would associate with the filament minus end, allowing this complex to add onto a free plus end +

  13. Effects of Thymosin and Protilin on Actin Polymerization

  14. Effects of Stathmin on Microtubules Stathmin’s binding to tubulin is inhibited by the phosphorylation of stathmin

  15. Organization of Microtubule Bundles MAP – Microtubule-associated protein MAPs have at least 1 domain that binds to the microtubule and another that projects outward

  16. Localization of MAPS in a Neuron -MAP2 protein stained orange in the cell body and dendrites -tau stained green in the axon

  17. Actin Filament Twisting Induced by Cofilin Cofilin – is a small protein that binds actin in a 1:1 ratio and destabilizes actin filaments Tropomyosin – an elongated protein that bind simultaneously to 7 actin monomers and stabilizes actin filaments

  18. Filament Capping Changes Filament Dynamics CapZ – Capping protein Capping is regulated by intracellular signals, PIP2 (Phosphatidylinositol 4,5-bisphosphate) uncaps + ends

  19. Proteins Binding Microtubule Ends Proteins that bind to the ends of microtubules can control microtubule positioning

  20. Cross-linking Cyoskeletal Elements Red – Microtubules Blue – Intermediate Filaments Green – Cross-linking protein, Plectin Plectin also links IF to actin filaments and microtubules Filaggrin bundles keratin filaments in the epidermis of the skin to give it its toughness

  21. Various Actin Arrays

  22. Actin Cross-linking Proteins

  23. Formation of 2 Types of Bundles

  24. A Micorvillus

  25. Filamin Cross-links Actin into a 3-Dimensional Network

  26. Loss of Filamin Causes Abnormal Cell Motility Actin formed by filamin is required for cells to extend the thin sheet-like membrane projections call lamellipodia

  27. Filament Severing Changes Filament Dynamics

  28. Microtubule Severing Red - Microtubules

  29. Actin Filament Severing by Gelsolin -Activated by high levels of cytoplasmic calcium -No energy needed -Gelsolin is removed by PIP2 Severing of microtubules by Katanin -made up of 2 subunits, one for severing and the other for targeting it -the process requires ATP

  30. Platelet Activation

  31. Platelet Activation

  32. Focal Contacts in Fibroblasts Focal contacts –highly specialized type of attachment between actin filaments and the extracellular matrix

  33. Effects of Extracellular Signals