Cytoskeleton

Question 1

What are actin filaments made from?

Answer 1

Actin polymer

Question 2

What are microtubules made of?

Answer 2

Alpha-beta tubulin dimers

Question 3

What are intermediate filaments made from?

Answer 3

Intermediate filament proteins

Question 4

What acin polymerises into F-actin?

Answer 4

G-actin

Question 5

How many other subunits does F-actin contact ?

Answer 5

Three, along the strand and between the two strands

Question 6

Structure of mysoin

Answer 6

• Myosin (class 2) is a hexameric protein:
• Two heavy chains dimerise (via the coiled coil) to form the coiled-coil tail
  and two globular myosin heads
• Each myosin head is composed of a motor domain and a lever.
• The lever contains 2 ‘IQ’ motifs (IQxxxRGxxR)
• Light chains bind to the IQ motifs – two per lever (two per heavy chain)
• Essential light chain (ELC) binds to an IQ motif close to the motor
• Regulatory light chain (RLC) binds to the IQ motif close to the coiled coil

Question 7

Hypertrophic cardiomyopathy (HCM)

Answer 7

Autosomal dominant, typical missense mutations in genes encoding sarcomeric proteins. Left ventricular hypertrophy and myofibrillar disarray

Question 8

Mutations in MYH7 cause what disease?

Answer 8

HCM

Question 9

Mutations in MYBPC cause what disease?

Answer 9

HCM

Question 10

Mutations in loop 1, converter and relay helix likely affect what?

Answer 10

Force generation

Question 11

Mutations in S2 affect

Answer 11

Interacting heads motif, more ATP usage. Could affect binding of MyBPC

Question 12

Mutations in non muscle myosin 2A cause these diseases

Answer 12

Blood clotting disorders, deafness and kidney disorder

Question 13

What does the activation of platelets depends on?

Answer 13

NM2A and actin

Question 14

What do smooth and non-muscle myosin 2 isoforms form?

Answer 14

10S shutdown state.

Question 15

What are smooth and noon-muscle myosins activated by?

Answer 15

Phosphorylation of the RLC

Question 16

Mutations in MYH9 cause what disorders?

Answer 16

Bleeding

Question 17

Mutations in skeletal muscle actins can cause

Answer 17

Skeletal muscle myopathies

Question 18

What mutations cause Baraitser-Winter syndrome?

Answer 18

Mutations in beta and gamma actins

Question 19

Symptoms of Baraitser-Winter syndrome

Answer 19

Changes around the eyes: (congenital ptosis
(drooping eyelid),
* High-arched eyebrows,
* Hypertelorism (increased eye spacing),
* Missing tissue around the eye (Ocular colobomata)
* Brain malformation - anterior predominant
lissencephaly.
* May also be short
* May also have microcephaly, intellectual disability, seizures and hearing loss

Question 20

What is critical to forming a highly folded brain?

Answer 20

Neuronal migration

Question 21

What is important for neuronal migration?

Answer 21

Non muscle actins

Question 22

Keratin is an example of what type of fibre?

Answer 22

Intermediate

Question 23

What filaments are required for cell to cell and cell-ECM adhesion?

Answer 23

Intermediate

Question 24

What happens in the skin epidermis basal layer?

Answer 24

Cells adhere to underlying extracellular
matrix through focal adhesions
(hemidesmosomes)
Cells divide (proliferate) - express K5
and K14
Then migrate upwards to spinous layer:
Switch keratin isoform expression to K1
and K10

Question 25

Mutations in keratin 5 and 14 cause

Answer 25

Epidermolysis bullosa

Question 26

mutations in Keratin 1 and 10 cause

Answer 26

Epidermolytic Hyperkeratosis

Question 27

What is found at the fast growing end of microtubule tubes?

Answer 27

Beta-tubulin which hydrolyses GTP, can exchange GDP for GTP.

Question 28

Do both alpha and beta tubulin bind GTP?

Answer 28

Yes

Question 29

Does beta tubulin hydrolyse GTP?

Answer 29

Yes, only.

Question 30

What part of microtubules can be PTM'ed?

Answer 30

C terminal tails

Question 31

What are microtubules essential for?

Answer 31

Cell migration, cargo transport, mitosis and formation of synapses and neuronal cells.

Question 32

What are the two types of motor proteins?

Answer 32

Kinesin and dynein

Question 33

How many types of kinesin are there?

Answer 33

Many, about 40, some specialised for trafficking like Kif5 (kinesin-1).

Question 34

How many types of dynein?

Answer 34

One, cytoplasmic.

Question 35

Which end does kinesin-1 move on microtubules?

Answer 35

Plus end

Question 36

Which end of microtubules does dynein move to?

Answer 36

Minus

Question 37

Description of TUBA1A mutation derived disease

Answer 37

Cause microcephaly, developmental delay, epilepsy, lissencephaly (smooth brain).

Question 38

What residue is commonly mutated in TUBA1A

Answer 38

R402

Question 39

What cell type are microtubules critical for?

Answer 39

Neurones

Question 40

What is KIF1A for?

Answer 40

Anterograde transport, veiscles for pre and post synaptic assmebly. Autophagy

Question 41

What is KIF1C for?

Answer 41

Anterograde cargo transport and retrograde transport between Golgi and ER

Question 42

What disease can Kif5A mutations cause?

Answer 42

Hereditary spastic paraplegia (SPG10), amytrophic lateral scleosis (ALS), Charcot-Tooth-Marie tyoe 2 (CMT2)

Question 42

Exon 27 deletion leads to what?

Answer 42

Aggregation