Slide 1Slide 2Slide 3Slide 4Slide 5Slide 6Slide 7Slide 8Slide 9Slide 10Slide 11Slide 12Slide 13Slide 14Slide 15Slide 16Slide 17Slide 18Slide 19Slide 20Slide 21Slide 2202.12.10Lecture 13 - Intermediate filamentsIntermediate 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 cellIntermediate filaments share a common structureIntermediate 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 microtubulesThere are 4 classes of intermediate filament proteinsTissue-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 cancerKeratin - the epithelial I.F.Stratified squamous epithelium•Stem cells in the interior•Dead cells at outermost surface•Keratin remains - hard, waterproof, resists abraisions•Makes up hair, nails, skin, & feathersKeratins form a strong network indirectly linked to neighboring cellsDesmosomes mediate cell-cell adhesion between epithelial cellsattachmentmembranesDesmosomes 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.Hemidesmosomes mediate cell-matrix adhesion between epithelial cells and basal laminaHemidesmosomes connect epithelial cells to the basal lamina. The integrin α β 4 binds to proteins in the plaques and to laminin in the extracellular matrix.Keratins allow sheets of cells to resist mechanical stressesDisruption of keratin networks causes blisteringVimentin/desmin - the I.Fs present in connective tissue and musclesVimentin is required for trans-epithelial migration• Endothelial transmigration - white blood cells leave the bloodstream to combat infection• Process is impaired in vimentin mutant miceDesmin 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 disordersNeurofilaments - I.F.s present in neuronsNeurofilaments 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 degeneratesNeurofilaments are important for nervous system functionNuclear 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 nucleusNuclear lamins disassemble when cells enter mitosisI.F.s are extensively cross-linked to actin and microtubules•Microtubule (red), vimentin (orange), plectin cross-linker
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