02.14.11 lecture 13 - intermediate filaments
TRANSCRIPT
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02.14.11Lecture 13 - Intermediate filaments
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Intermediate filaments
• Present in nearly all animals, but absent from plants and fungi
• Rope-like network of filaments in the cell
• Principle function is maintenance of cell structure - provide tensile strength to the cell
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Intermediate filaments share a common structure
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Intermediate filaments differ from actin & microtubules:
• I.F.s do not have a defined polarity (I.e. no plus or minus ends)
• I.F.s have no associated motor proteins
• I.F.s do not bind to nucleotides (ATP or GTP)
• I.F.s are very stable compared to actin or microtubules
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There are 4 classes of intermediate filament proteins
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Tissue-specific expression of I.F. proteins is useful for diagnostics
• Cancer cells - lose the characteristic shape of the parent tissue
• I.F. gene expression is often unaffected
• Identification of I.F. proteins in tumor biopsies using antibodies can pinpoint origin of tumors (I.e. neurofilaments in metastatic cells from brain cancers)
• Physicians tailor treatment to particular types of cancer
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Keratin - the epithelial I.F.
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Stratified squamous epithelium
• Stem cells in the interior
• Dead cells at outermost surface
• Keratin remains - hard, waterproof, resists abraisions
• Makes up hair, nails, skin, & feathers
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Keratins form a strong network indirectly linked to neighboring cells
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Desmosomes mediate cell-cell adhesion between epithelial cells
attachment
membranes
Desmosomes are formed in specialized areas of cells - the cytoplasmic side contains tonofibrils that are anchored in a plaque of proteins.
Cadherin molecules provide the cell - cell interactions.
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Hemidesmosomes mediate cell-matrix adhesion between epithelial cells and basal lamina
Hemidesmosomes connect epithelial cells to the basal lamina. The integrin α6β4 binds to proteins in the plaques and to laminin in the extracellular matrix.
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Keratins allow sheets of cells to resist mechanical stresses
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Disruption of keratin networks causes blistering
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Vimentin/desmin - the I.Fs present in connective tissue and muscles
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Vimentin is required for trans-epithelial migration
• Endothelial transmigration - white blood cells leave the bloodstream to combat infection• Process is impaired in vimentin mutant mice
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Desmin filaments maintain muscle structural integrity
• Desmin filaments are tethered to the Z disk and evelope the sarcomere
• Don’t participate in contraction, but maintain structural integrity
• Mutant mice have misaligned muscle fibers
• Mutations in human desmin causes muscle disorders
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Neurofilaments - I.F.s present in neurons
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Neurofilaments are important for nervous system function
• Unlike other I.F.s, they have side arms that project from the core filament
• Fill and pack the cytoplasm of neurons
• Neurons in KO mice make axons with smaller diameters
• Charcot-Marie-Tooth disease: neuropathy where PNS degenerates
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Neurofilaments are important for nervous system function
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Nuclear lamins are I.F.s present in the nuclei of all cells
• Nuclear lamins form a basket-like structure on inner side of nuclear membrane
• Protects structure of nucleus
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Nuclear lamins disassemble when cells enter mitosis
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I.F.s are extensively cross-linked to actin and microtubules
• Microtubule (red), vimentin (orange), plectin cross-linker (blue)