Microbiology 10: (Shackleton) Intermediate Filaments

Question 1

Categories of intermediate filaments (IFs)? Where are they found?

Answer 1

Lamins - nuclei
Keratins - Epithelial cells
Vimentin - Fibroblasts
Neurofilaments - Neurons
Desmin - Muscle cells

Question 2

IF general structure?

Answer 2

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

Question 3

Characteristics/properties of IFs?

Answer 3

• 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

Question 4

Describe nuclear lamin function

- how was the function determined?

Answer 4

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)

Question 5

Describe Inherited disorders caused by Lmna mutation? Why so many?

Answer 5

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)

Question 6

Describe keratin structure - how do they interact with desmasomes

Answer 6

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)

Question 7

Mutations in keratin genes result in what?

Answer 7

Skin blistering diseases e.g. Epidermolysis bullosa simplex (weakened epithelial links)

Question 8

What are neurofilaments? Types? Function?

Answer 8

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

Question 9

Mutations in neurofilament genes lead to what? Example ?

Answer 9

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)