1 / 24

Molecular Cell Biology

Molecular Cell Biology. Intermediate Filaments Cooper. Introduction. Filaments 10 nm wide => “intermediate” Present in Metazoa / Animals i.e. not Plants or Unicellular Organisms Complex Gene Superfamily 70 in Human Genome Specific Expression at Different Times and Places.

jihan
Télécharger la présentation

Molecular Cell Biology

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Molecular Cell Biology Intermediate Filaments Cooper

  2. Introduction • Filaments 10 nm wide => “intermediate” • Present in Metazoa / Animals • i.e. not Plants or Unicellular Organisms • Complex Gene Superfamily • 70 in Human Genome • Specific Expression at Different Times and Places

  3. Intermediate Filament Biochemical Properties In Vitro • Very stable. Little subunit exchange. • Very strong. Filaments do not break. • MT’s strong but brittle • Actin weak

  4. Intermediate FilamentPotential Functions In Vivo • Mechanical Strength of Cytoplasm • Help a Layer of Epithelial Cells Resist Shear Stress - Filaments Connect to Cell-cell Junctions • Hold Nucleus in Center of Cell

  5. IntermediateFilamentStructure &Assembly

  6. Intermediate Filaments by EM:Filament Unraveling

  7. Classes of Intermediate Filaments

  8. Regulation of IF Assembly • Notoriously Stable • No Nucleotide • Filaments Move Little • Precursors Move More • Disassemble Somewhat during Mitosis • Phosphorylation by Cyclin-depen Kinase

  9. Vimentin Filaments in a Cultured Cell

  10. Vimentin • All Cells in Early Development • Cage Around Nucleus • Interacts with Mt’s • Vimentin Knockout Mouse • Initially normal at gross inspection • Cultured cells have altered properties of uncertain significance

  11. FRAP of Vimentin vs. Keratin in One Cell Left: Vimentin (Green) Right: Keratin (Red) 10 min time intervals

  12. Dynamics of Keratin Particles in Periphery 11 micrometers over 10 minutes 18 micrometers over 10 minutes

  13. Desmin • Expressed in Muscle • Elastic Elements to Prevent Over-stretching • Connects / Aligns Z lines • Knockout Mouse - Deranged Myofibril Architecture

  14. Keratins • Expressed in Epithelia • Keratin Filaments Connect to Desmosome and Hemidesmosomes • Differentiation of Epidermis includes Production of Massive Amounts of Keratin • Provides Outer Protection of Skin • Composes Hair, Nails, Feathers, etc.

  15. Density of Keratin Filaments in Outer Epidermis Layers

  16. Keratin Mutations are Basis forHuman Epidermal Diseases • Structure/Function Analysis of Keratin Assembly • Point Mutation in Terminal Domain Fails to Assemble • Mutant is Dominant, even in Low Amounts, in Cultured Cells and Mice

  17. Epidermolysis Bullosa Simplex Wild-type Mutant

  18. Keratins and EBS

  19. Neurons • Neurofilament H, M, L Copolymer • Prevent Axon Breakage • Diseases with Clumps of Neurofilaments • Superoxide dismutase model for ALS • Clumps are secondary, not causative

  20. Neurofilament Transport in Axons Photobleached Zone in the Middle

  21. Neurofilament Transport in Axons Photobleached Zone in the Middle

  22. Lamins • Square Lattice on Inner Surface of Nuclear Membrane • Present in Metazoans (Animals, not Plants or unicellular organisms) • Mitosis Breakdown • Phosphorylation of A & C by Cyclin-depen Kinase • B remains with Membrane • Mutations Cause Accelerated Aging Diseases • Progerias - Dominant Mutations

  23. EM of Nuclear Lamina Nuclear Pores

  24. End

More Related