Microbiology 10: (Shackleton) Intermediate Filaments Flashcards
Categories of intermediate filaments (IFs)? Where are they found?
Lamins - nuclei Keratins - Epithelial cells Vimentin - Fibroblasts Neurofilaments - Neurons Desmin - Muscle cells
IF general structure?
Conserved structure with a central alpha-helical domain that promotes dimerisation
Head domain - Rod - Tail domain
separated by rod (alpha-helical domain) coiled coils
Dimers can polymerise to form tetramers, eight tetramers to form filaments
filaments NOT POLAR in nature
Characteristics/properties of IFs?
- Filaments are non-polar
- More stable (less dynamic) than actin, microtubules
- Bend easily but very difficult to break
- Have great elastic properties
- Prominent in cell types subject to mechanical stress e.g. skin, muscle
- IFs provide cells with tensile strength + resistance to mechanical strain
Describe nuclear lamin function
- how was the function determined?
Form a proteinacious meshwork underneath the nuclear envelope - the nuclear lamina
Provides structural support to the nuclear envelope
Organises nuclear contents, including chromatin
Lmna knockout mice showed malformed chromatin organisation, nuclear lamina (showed function)
Describe Inherited disorders caused by Lmna mutation? Why so many?
Laminopathies
Emery-Dreifuss muscular dystrophy
- abnormally shaped nuclei susceptible to rupture through weakening of nuclear lamina
Partial lipodystrophy
Hutchinson-Gilford progeria syndrome
- proteins retain farensyl lipid group in mutation -> causes thickened lamina, loss of elastic properties and early cell senescence
Causes so many diseases due to LaminA/C proteins contributing to most nuclear processes (different mutations have different interactions)
Describe keratin structure - how do they interact with desmasomes
Formed of heterodimers of acidic and basic/neutral chains
Disulphide bonds cross-link the filaments forming very strong networks
- cysteine comprises 14% of residues in hair keratins
Keratins strengthen epithelia through desmosomes/hemi-desmosomes
- Connections between neighbouring cells and with the basal lamina
- (desmin plays similar role in heart muscle)
Mutations in keratin genes result in what?
Skin blistering diseases e.g. Epidermolysis bullosa simplex (weakened epithelial links)
What are neurofilaments? Types? Function?
Found in neurons - provide tensile strength to axons
3 types
NF-L (Light), NF-M (Medium), NF-H (Heavy)
- NF-L forms heterodimers with the 2 other types
Mutations in neurofilament genes lead to what? Example ?
Neurodegenerative disorders
e. g. Charcot-Marie-Tooth disorder
- Peripheral Neuropathy
- Neurofilament disruption leads to peripheral axon degeneration
- Causes progressive weakening + loss of function
of some muscles in foot (because longest axons found here)