32: Contractile Proteins Flashcards

1
Q

Dystrophin function

A

Links muscle fiber cytoskeleton + ECM/basal lamina; acts as a shock absorber for contraction, stabilizes sarcolemma

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2
Q

Dystrophin structure

A

Super big; 427 kDa (largest human gene, 79 Exons), has numerous redundant coils

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3
Q

What are 2/3rds of all dystrophin mutations

A

Large internal deletions

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4
Q

Out of frame vs in-frame dystrophin mutation

A

Out of frame -> frameshift -> DMD

In frame -> BMD

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5
Q

Genetics of DMD

A

X-linked recessive, affecting 1 in 3,500 boys

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6
Q

A few treatment options for DMD

A

Gene therapy, dystrophin replacement, drugs to prevent exon skipping

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7
Q

G actin structure

A

375AA polypeptide divided into two lobes, with an ADP or ATP bound to the bottom of the cleft, connecting the lobes

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8
Q

F actin

A

Tight right-handed helix formed by two strands of G actin polymerizing

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9
Q

Why is polarity of actin important?

A

For determining which way myosin moves along it

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10
Q

Three steps of actin filament assembly

A
  1. Nucleation
  2. Elongation phase
  3. Steady state
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11
Q

Nucleation of actin

A

3 G-actin monomers aggregate into an oligomer

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12
Q

ATP hydrolysis in actin formation

A

ATP is bound to monomers -> hydrolyzed to ADP + Pi following filament assembly

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13
Q

Where are actin filaments particularly abundant in the cell?

A

Beneath plasma membrane

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14
Q

A requirement for actin binding proteins

A

Must have at least two actin-binding domains (ABDs)

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15
Q

Actin bundles vs actin networks

A

Actin bundles: cross-linked into parallel arrays (filament polarity aligned)
Actin networks: loosely cross-linked into orthogonal arrays (polarity doesn’t align)

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16
Q

Two types of actin bundles and the protein that holds them together

A
  1. Parallel bundles: fimbrin

2. Contractile bundles: a-actinin

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17
Q

Parallel vs contractile bundles of actin: packing

A

Parallel bundles: tight packing -> prevents myosin II from entering
Contractile bundles: loose packing, allowing myosin II to enter for contraction

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18
Q

Parallel bundle function

A

Supports projections of plasma membrane, increases cell surface, structural stability, allows for additional receptors to be placed on plasma membrane

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19
Q

Example of parallel bundles vs contractile bundles

A

Parallel: microvilli
Contractile: contractile ring in mitosis

20
Q

Actin network function

A

Forms 3D meshwork for flexible, gel-like properties

21
Q

Example of a protein that holds actin networks together

A

Filamen

22
Q

Spectrin

A

An actin binding protein in plasma membrane of RBCs that creates a cortical cytoskeleton

23
Q

Two other proteins that assist spectrin

A

Ankyrin, protein 4.1

24
Q

HS mutation

A

Spectrin, ankyrin, protein 4.1

25
Q

What happens in hereditary Spherocytosis?

A

RBCs are spherical and have impaired deformity, reduced stability, difficult to enter capillaries -> membranes break down and RBCs die -> anemia, jaundice, splenomegaly

26
Q

Three domains of myosin and their functions

A
  1. Head: binds actin and ATP
  2. Neck: binds myosin light chain
  3. Tail: intertwine to bring heads closer, bind membranes/organelles
27
Q

Powerstroke mechanism and neck of myosin

A

Longer neck -> proportional to powerstroke mechanism movement

28
Q

What direction on actin do myosin I, II, and V move towards?

A

Plus end

29
Q

Myosin I, II, and V structures

A

I: 1 heavy chain + head + neck
II: 2 heavy chains + 2 heads + 2 necks
V: 2 heavy chains + 6 light chains per neck

30
Q

Only single-headed myosin

A

Myosin I

31
Q

Myosin I function

A

Some associate directly with membranes through tail-lipid interaction

32
Q

Only myosin class that can assemble into bipolar filaments through tail interactions

A

Myosin II

33
Q

Myosin V function

A

Tails associate with organelles/cargo -> carry it along actin filament tracks

34
Q

Four important functions of myosin-powered movements

A
  1. Skeletal muscle contraction
  2. Smooth muscle contraction
  3. Non-muscle cell contraction
  4. Cell migration
35
Q

Titin structure and function

A

Attaches Z disc -> middle f myosin filament; stabilizes myosin and prevents overstretching, brings thick filament back to baseline after contraction

36
Q

What do mutations in titin cause?

A

Cardiomyopathies

37
Q

Components of thin filaments

A

Actin, troponin, tropomyosin

38
Q

Nebulin

A

Long protein wrapping around actin, determines length of thin filament

39
Q

What two proteins stabilize ends of actin?

A

CapZ: stabilizes + end
Tropomodulin: stabilizes - end

40
Q

What constantly pumps Ca from Cytosol into SR in a resting muscle?

A

SERCA; SR Ca ATPase

41
Q

Smooth muscle contraction steps

A
  1. Ca levels rise, Ca binds calmodulin
  2. Calmodulin activates MLCK
  3. MLCK phosphorylates myosin light chains -> high affinity for actin
  4. Powerstroke
42
Q

What happens when Ca levels drop after smooth muscle contraction?

A

MLCK becomes inactive, MLCP dephosphorylates myosin light chains -> low affinity state for actin -> relaxation

43
Q

Non muscle cell actin-myosin structures

A

Can transiently form actin-myosin structures similar to skeletal muscle as needed, but are less stable and less organized

44
Q

Cytokinesis

A

Bundles of F-actin and myosin II form a contractile ring -> cleavage furrow

45
Q

What factor is expressed in fibroblasts for the localization of actin, causing cell migration?

A

GFP-actin