Fig Intermediate Filaments

Transcription

1 Fig Intermediate Filaments

2 Overview: Intermediate filaments are easily bent and stretched but highly resistant to breaking. They provide mechanical strength to cells. Unlike actin filaments and microtubules, intermediate filaments perform specialized functions and are not expressed in all organisms or all cell types within an individual organism.

3 Intermediate Filaments are molecularly strong Fig 16-9

4 Formation of intermediate filaments: Intermediate filament monomers contain a long alpha helical domain Alpha helical domains allow formation of a coiled-coil dimer Dimers are linked in a head-to-tail manner, forming a tetramer Tetramers form protofilaments, Eight protofilaments are joined to form an individual intermediate filaments Fig 16-19

5 Formation of intermediate filaments cont: Fig Individual filaments can be bundled or crosslinked into larger structures Additional points: Intermediate filaments are non-polarized No motor proteins use intermediate filaments No energy needed: Intermediate filament monomers polymerize readily in solution without accessory proteins Non phosphorylated intermediate filament subunits assemble. Disassembly of intermediate is accomplished by phosphorylation

6 Organization of intermediate filaments: Fig Fig Neurofilament intermediate filament proteins can bundle themselves (left) Intermediate filaments can also be bundled by association with plectin (green), a protein that also associates with intermediate filaments (blue) and microtubules (red).

7 Disassembly of microtubules causes collapse of the intermediate filament network Effects of the drug nocodazole on microtubule Effects of the drug nocodazole on intermediate filaments Martys et al., Mol Biol Cell May; 10(5):

8 Intermediate filaments are dynamic Fluorescence Recovery after Photobleaching of GFP-vimentin in living cells GFP-vimentin dynamics in living cells Martys et al., Mol Biol Cell May; 10(5):

9 Table 16-1 Major types of intermediate filaments in vertebrate cells Type of IF Component Polypeptides Cellular Localization Number of Genes Nuclear Lamin Nuclear lamina (inner lining of nuclear envelope) 3 or more (A,B,C..) Vimentin-Like Vimentin Cells of mesenchymal origin (fibroblasts, bone, blood etc) 4 or more Desmin Glial Fibrillary Acidic Protein (GFAP) Muscle Glial cells (astocytes and schwann cells in nervous system) Epithelial Keratins Epithelial cells and their derivatives (hair, nails) 15 or more 15 or more Axonal Neurofilaments neurons 3 or more (H,M,L..) Table 16-1

10 Nuclear lamins: nucleus Panel 16-1 Phosphorylation of nuclear lamins disassembles the nuclear envelope during mitosis. Dephosphorylation of lamins causes reassembly at the end of mitosis. Ellenberg, et al., 1997). J. Cell Biol., 138,

11 Vimentin like proteins Vimentin in a sheep kidney fibroblast. The University of Auckland, NZ Vimentin: mesenchymal tissues (blood, bone, muscle)

12 Confocal immunofluorescence imaging of desmin in cardiomyocytes. Appaix et al., Exp Physiol (2003) Vimentin like proteins: Desmin

13 Vimentin like proteins GFAP in astrocytes GFAP in immature astrocytes. Prof Fred Sablitsky, The University of Nottingham, Institute of Genetics Glial fibrillary acidic proteins (GFAP) :supporting cells of the central and peripheral nervous system

14 Mutation in GFAP proteins causes Alexander disease Grey Matter w/ Rosenthal fibers. Wippold et al., American Journal of Neuroradiology 27: , May 2006 MR imaging of a patient with biopsy-confirmed infantile Alexander disease. Van der Knaap et al., American Journal of Neuroradiology 22: (3 2001)

15 Keratins: epithelial cells and derivatives (hair, nails) Antikeratin staining in epithelial cells spines of IFs in skin keratin filaments (most diverse family of subunits) are found in epithelial cells.

16 Keratin genetic deficiencies Epidermolysis bulosa symplex Fig Dermatology Information System

17 Neurofilaments (neurons) neurofilaments - found in neurons and form cytoskeleton of axons and dendrites The number of neurofilaments determines the diameter of axon and the speed of impulse NFH (red) in human SHSY5Y neuroblastoma cells

18 Neurofilaments (neurons) Lou Gehrig's Batting Average IFs in normal (above) and amyotrophic lateral sclerosis disease (ALS or Lou Gehrig s) (below) brain tissue