Intermediate Filaments Text and image sources are included using the notes function of this file Cytokeratin Mitochondria DNA.

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Presentation transcript:

Intermediate Filaments Text and image sources are included using the notes function of this file Cytokeratin Mitochondria DNA

The IMF Family TypeProteinHuman gene #Mol WeightCell type Type I (acidic) Type II (basic)Keratins> kDa kDaEpithelia Type III (vimentin-like)Vimentin Desmin GFAP Peripherin kDa 54 kDa 50 kDa 57 kDa Mesenchymal cells Muscle Glia, astrocytes PNS neurons Type IV (neurofilaments)NF-L NF-M NF-H [alpha]- internexin kDa 102 kDa 110 kDa 66 kDa CNS neurons CNS neurons Type V (nuclear lamina)Lamins A / C Lamins B 1, B ea 70/63 kDa 67/72 kDa Nucleus - Mature cells Nucleus - Develop.cells * Lens (Type VI)Phakinin/CP49 Filensin1 49 kDa 95 kDaLens Others:Nestin, Synemin, Paranemin, Plasticin, Tanabin... (Prokaryotic IMF family member)(Cresecntin)(Prokaryotes) form heterodimers

Assembly as simple as abcdefg central rod domain bundles of 8 tetramers

Atomic Model of the Dimer

Keratins Lamins Cytokeratins in Epithelial Cells

Epidermolysis Bullosa Simplex arises from keratin point mutations Dowling-Meara - widespread blistering Koebner - blistering confined to hands and feet Weber-Cockayne - least severe

Stretching an EBS cell destroys the keratin cytoskeleton

Vimentin in Fibroblasts

Cancer detection Cytokeratins are normally expresssed in skin but not in the underlying tissues. Antibody staining can reveal hyperplasia and metastasis of epithelial cells into those tissues as a cancer progresses. Normal Skin Squalous cell carcinoma

Neurofilaments in Neurons NF-H in neurons GFAP in glia

Active Remodeling (note - short clips are repeated several times in each part of the sequence)

Cytokeratin- GFP dynamics 4 hour sequence

Cytokeratin-GFP dynamics during mitosis 40 minute sequence

Okadaic acid (phosphatase inhibitor) results in cytokeratin disassembly 200+ minute sequence Cytokeratin 13::GFP

Cytokeratin-GFP dynamics require ATP 96 minute sequence

Cytokeratin- GFP dynamics requires microtubules 115 minute sequence

Microinjection of anti-detyrosinated tubulin antibodies collapses the IMF network

Cytokeratin- GFP dynamics doesn’t require micro- filaments 115 minute sequence

Vimentin-GFP Time-lapse Close-up cell edge Nocodazole collapse

Vimentin overlays Distinct from Microfilaments Co-align with Microtubules

Plectin links Vimentin IMFs and Microtubules

The Cytomatrix

Tensegrity F-actin

The Axonal Matrix

Murine Macrophage

Nocodozole- treatment depolymerizes mts and causes lamellipodial retraction

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