Lecture 4. The cytoskeleton III - Intermediate Filaments Flashcards
Describe the intermediate filaments appearance ?
Its a rope like structure with a diameter of 10nm. Its the toughest and most durable filaments of the cytoskeleton.
Where are intermediate filaments abundant ?
Cytoplasms of cells which are subject to mechanical stress. For example, muscle cells, epithelial cells of the skin and long nerve cell axons.
How many proteins can develop into intermediate filaments ?
Over 70
What and why do intermediate filaments form in cytoplasm of animal cells ?
They form networks in the cytoplasm of most animal cells to give cells mechanical strength
Where can intermediate filaments be found ?
- Cytoplasm of cells subject to mechanical stress
2. Nucleus
What and why do intermediate filaments form in the nucleus ?
The nuclear lamins form a mesh like structure under the nuclear envelope of eukaryotic cells which provides strength to the nucleus
What gives intermediate filaments their mechanical strength and durability ?
Their structural composition
Describe the structure of an intermediate filament ?
- Intermediate protein monomers have a central rod domain with globular regions at each end.
- Monomer pairs associate to form a dimer.
- Two dimers associate in an anti-parallel manner to form a staggered tetramer.
- Tetramers further assemble end to end.
- 8 assemble side by side and twist to form the final rope like filament.
What do all intermediate filaments proteins have ?
They are elongated fibrous molecules that have an N-terminal head domain, a central rod domain and a C-terminal tail domain
What is a central rod domain ?
a central rod domain comprises of some 300 to 350 residues which is arranged in coiled alpha-helices, with at least two short characteristic interruptions; a N-terminal non-helical domain (head) of variable length; and a C-terminal domain (tail) which is also non-helical, and which shows extreme length variation between different intermediate filament proteins.
Why can intermediate filaments when they associate with each other all form filaments of similar diameter ?
Similar rod domain structures
What can vary from one intermediate filament to another ?
The globular head and tail regions of protein monomers exposed on the surface of a filament.
What allows the intermediate filament to interact with other components of the cell ?
The head and tail domain region
How many types of intermediate filament proteins are there ?
6
What are type I and type II intermediate filament proteins ?
They consist of acidic and basic epithelial keratins. (54 genes). An acidic type I and basic type II keratin dimerise to form keratin filament structures which are only found in the cytoplasm of epithelial cells.
Where are keratin filament structures only found ?
The cytoplasm of epithelial cells
What are type III intermediate filament proteins ?
They are the vimentin and vimentin related intermediate filaments. They are found in the cytoplasm of connective tissues, muscle cells and glial cells.
What are they classes of type III intermediate filaments ?
- vimentin
- desmin
- perpherin
- glial fibrillary acidic factor (GFAP)
- syncoilin
What are type IV intermediate filaments ?
These are neurofilament proteins referred to as heavy, medium or low depending on their molecular weights and two other proteins internexin and nestin
What is the function of internexin and nestin ?
Give structural support
What are desmosomes responsible for ?
Cell to cell contacts
What is the benefit of desmosomes ?
Gives strength to cell connections
What are hemidesmosomes responsible for ?
Connect the cell to the underlying cell matrix beneath
What is a cadherin ?
A transmembrane protein
How do cadherins proteins associate ?
Via their extracellular domains to hold adjacent cells together
How desmosomes structurally link to keratin intermediate filaments of a cell to those of its neighbouring cell ?
The cytoplasmic surface of each membrane has a dense plaque which consists of anchoring proteins and these tightly bind to the bundle of keratin filaments and cadherins
What are type V intermediate filaments ?
They form a meshwork of intermediate filaments under the nuclear envelope. The lamins are directed to the nucleus via their nuclear localisation sequence and must disassemble and reassemble at every cell division, when the nuclear envelope breaks down.
What are two type VI intermediate filaments proteins ?
- filensin
2. phakinin
What are type VI intermediate filament proteins ?
Filensin and phakinin co-assemble to form unique beaded filament structures which are highly specific to the eye lens and maintain lens transparency
How many type I acidic keratins is there ?
28
How many type II basic keratins is there ?
26
What is the difference between heterodimers and homodimers ?
Only heterodimers of keratin can form dimers, not homodimers
What are the three groups of keratin pairs ?
- Simple eg. intestinal
- Barrier eg. cornea
- Structural eg. hair
What is epidermolysis bullosa simplex ?
- A human genetic disease which mutates the keratin (K5, K14) genes. 2. Its autosomal dominant and causes fragile skin and recurrent blister formation
What does desmin do in muscle ?
Stabilises sarcomeres by forming a lattice of a band of desmin around it, maintaining muscle integrity
What do desmin filaments encircle ?
the z disc and are cross linked to the PM
What do longitudinal desmin filaments do ?
They cross neighbouring z discs in myofibril and connect desmin around z discs in adjacent myofibrils, cross linking them into bundles.
What is desmin myopathy ?
Progressive disorder of skeletal, cardiac and smooth muscle
