The Cytoskeleton II

Question 1

What are the 3 main types of actin?

Answer 1

a, B and Y

Question 2

What is G and F-actin?

Answer 2

G = globular
F = filamentous
G polymerises into F in a process which requires ATP

Question 3

What helps the conversion of ADP to ATP in actin formation?

Answer 3

Profilin

Question 4

What are the two subfragments of myosin called?

Answer 4

S1 and S2, together make heavy meromysin

Question 5

What does the tail of myosin form?

Answer 5

A coiled-coil

Question 6

What does Titin do?

Answer 6

Regulates the length of myosin

Question 7

What does tropomodulin do?

Answer 7

Caps F-actin at the barbed end by Cap-Z pointed end

Question 8

What is cardiomyopathy?

Answer 8

Caused by mutations in sarcomeric proteins in the myosin heavy chain, normally autosomal dominant missense mutations. The first symptom could be death

Question 9

What is hypertrophic cardiomyopathy?

Answer 9

The disease of the muscle sarcomere, causes progressive heart failure

Question 10

What is a common mutation, found in the actin binding domain of motor

Answer 10

R403Q

Question 11

What does R403Q do?

Answer 11

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

Question 12

Where are congenital myopathies?

Answer 12

Skeletal muscle, mutations in the thin filament actin and nebulin

Question 13

How do actin myopathy mutations cause a phenotype?

Answer 13

Affect nucleotide binding and exchange, will affect filament formation

Question 14

How do intracellular rod mutations cause a phenotype?

Answer 14

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

Question 15

How do nemaline myopathy mutations cause a phenotype?

Answer 15

Not clustered, will have a variety of effects including effects on polymerisation

Question 16

What can intracellular rod mutations do?

Answer 16

Result in actin developing in the nucleus because it is not being cycled out by profilin, mutations prevent this binding

Question 17

What is the actin cytoskeleton in non-muscle cells require for?

Answer 17

Cell-cell adhesion and migration

Question 18

Give three examples of diseases caused by mutations in actin?

Answer 18

1. Blood clotting disorders
2. Deafness and blindness
3. Pigmentation diseases

Question 19

What is activity of NM2A regulated by?

Answer 19

Light chain phosphorylation, causes the molecule to unfold and form filaments (Active)

Question 20

What can NM2A mutations result in?

Answer 20

Enlarged platelets, blood clotting disorders.

Question 21

What is D1424?

Answer 21

The region of the tail that interacts with the head in the folded inactive molecule

Question 22

What is mouse model shaker 1?

Answer 22

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.

Question 23

What is griscelli syndrome?

Answer 23

Pigmentation defects caused by mutations in Myo5a as transport of melanosomes is affected resulting in patchy pigmentation in hair and skin

Question 24

Give 4 types of intermediate filament and where they are found

Answer 24

1. Keratin - epithelial
2. Desmin - muscle
3. Vimentin - Fibroblasts
4. Neuronal - neurones

Question 25

What are intermediate filaments required for?

Answer 25

Cell-Cell and Cell-ECM adhesion

Question 26

What is epidermolysis bullosa?

Answer 26

Keratin mutations

Question 27

What do mutations in desmin effect?

Answer 27

Skeletal, cardiac and smooth muscle, main problem in the heart because heart cells need to attach to each other strongly.

Question 28

What are nuclear lamins?

Answer 28

A class V intermediate filament, cause laminopathies.