The Cytoskeleton II Flashcards
What are the 3 main types of actin?
a, B and Y
What is G and F-actin?
G = globular
F = filamentous
G polymerises into F in a process which requires ATP
What helps the conversion of ADP to ATP in actin formation?
Profilin
What are the two subfragments of myosin called?
S1 and S2, together make heavy meromysin
What does the tail of myosin form?
A coiled-coil
What does Titin do?
Regulates the length of myosin
What does tropomodulin do?
Caps F-actin at the barbed end by Cap-Z pointed end
What is cardiomyopathy?
Caused by mutations in sarcomeric proteins in the myosin heavy chain, normally autosomal dominant missense mutations. The first symptom could be death
What is hypertrophic cardiomyopathy?
The disease of the muscle sarcomere, causes progressive heart failure
What is a common mutation, found in the actin binding domain of motor
R403Q
What does R403Q do?
Force of muscle contraction is decreased as there is increase in the speed of tension and also relaxation. Less time is spent in a force generating state
Where are congenital myopathies?
Skeletal muscle, mutations in the thin filament actin and nebulin
How do actin myopathy mutations cause a phenotype?
Affect nucleotide binding and exchange, will affect filament formation
How do intracellular rod mutations cause a phenotype?
Mutations near the ATP cleft cause actin myopathy like symptoms. Can affect filament polymerisation, actin-actin interactions within the filament and removal of actin from the nucleus
How do nemaline myopathy mutations cause a phenotype?
Not clustered, will have a variety of effects including effects on polymerisation
What can intracellular rod mutations do?
Result in actin developing in the nucleus because it is not being cycled out by profilin, mutations prevent this binding
What is the actin cytoskeleton in non-muscle cells require for?
Cell-cell adhesion and migration
Give three examples of diseases caused by mutations in actin?
- Blood clotting disorders
- Deafness and blindness
- Pigmentation diseases
What is activity of NM2A regulated by?
Light chain phosphorylation, causes the molecule to unfold and form filaments (Active)
What can NM2A mutations result in?
Enlarged platelets, blood clotting disorders.
What is D1424?
The region of the tail that interacts with the head in the folded inactive molecule
What is mouse model shaker 1?
Mutations in Myo7a show how stereocilia become highly disorganised resulting in deafness. As it is also important for pigment trafficking in the retina it can also cause blindness.
What is griscelli syndrome?
Pigmentation defects caused by mutations in Myo5a as transport of melanosomes is affected resulting in patchy pigmentation in hair and skin
Give 4 types of intermediate filament and where they are found
- Keratin - epithelial
- Desmin - muscle
- Vimentin - Fibroblasts
- Neuronal - neurones
What are intermediate filaments required for?
Cell-Cell and Cell-ECM adhesion
What is epidermolysis bullosa?
Keratin mutations
What do mutations in desmin effect?
Skeletal, cardiac and smooth muscle, main problem in the heart because heart cells need to attach to each other strongly.
What are nuclear lamins?
A class V intermediate filament, cause laminopathies.
