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BMS2.15 Cytoskeleton 2 > Cytoskeleton 2 > Flashcards

Cytoskeleton 2 Flashcards

1
Q

Lamellipodium:

A
  • a protrusion at the leading edge of a migrating cell.
    • caused by actin polymerization
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2
Q

Two parts of cell migration via actin polymerization:

A
  • formation of lamellipodium at the leading edge due to actin polymerization.
  • collapse of the cell tail by actin depolymerization due to myosin II.
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3
Q

Contractile Ring:

A
  • the ring formed during cytokinesis whe two cells are dividing.
  • formed by actin and myosin II.
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4
Q

Adhesion belts:

A
  • contractile bundles of actin and myosin filaments near the apical surface of epithelial cells.
  • important for morphogenesis:
    • myosin II contraction drives tissue invagination and formation of the neural tube.
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5
Q

The three classes of cytoskeletal motors:

A
  • dynein
  • kinesin
  • myosin

all are ATPases and have multiple isoforms, encoded by multiple genes

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6
Q

Kinesins:

A
  • carry cargo from the centrosome (minus end) to the periphery (plus end) on microtubules
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7
Q

Dyneins:

A
  • carry cargo from the periphery (plus end) to the centrosome (minus end) on microtubules.
  • much larger than kinesins
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8
Q

Myosins:

A
  • move cargo on actin
  • most move from the minus end to the plus end
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9
Q

Dynein, kinesin, and myosin are all:

A

ATPases

“mechanochemical enzymes”

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10
Q

What two motors are related structurally and mechanistically?

A

kinesin and myosin

however, have different functions

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11
Q

Particular isoforms of cytoskeletal motors …

A
  • only move in one direction on an actin filament or microtubule.
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12
Q

Molecular/cytoskeletal motors are the downstream targets of:

A

signaling cascades

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13
Q

How do molecular motors function/move on a filament?

A
  • They are enzymes (ATPases)
    • Chemical energy from binding/hydrolysis of ATPase leads to:
    • → intramolecular conformational change
    • → mechanical work
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14
Q

What is the work done by molecular motors?

A
  • generation of tension or movement of an object along an actin filament or microtubule
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15
Q

Do intermediate filaments have motors?

A

NO

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16
Q

Myosin structure:

A

tail → neck/hinge → light chains → motor/head

  • Globular “head” is the motor domain; contains ATPase.
  • Variable “Tail” domain contains coiled coil for dimerization, and/or binds to membrane or target vesicle.
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17
Q

Classification of myosins is based on:

A
  • motor domain (“head”) homology
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18
Q

Kinesin head domains are structurally related to:

A

myosin and G-proteins

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19
Q

Kinesin Structure:

A

tail → stalk → neck → motor/head

20
Q

What portion of the kinesin determines its polarity?

A

the neck region next to the motor/head domain

21
Q

What part of the kinesin contains the light chains?

A

the tail region

22
Q

Kinesin N-terminal motors have what polarity:

A

plus-end directed

23
Q

Kinesin C-terminal motors have what polarity:

A

minus-end directed

24
Q

What two molecular motors have large gene families?

A

myosin and kinesin

25
Q

Dynein motors:

A
  • ATPase
  • minus-end directed
  • multi-subunit protein
26
Q

Dynein is what kind of protein:

A
  • AAA protein
    • “ATPase Associated with diverse cellular Activities”
  • Typically 6 domains
  • ATPase domain connected to a microtubule via a stalk

ATPase NOT DIRECTLY ATTACHED TO MICROTUBULE

27
Q

Primary ciliary dyskinesia (PCD)

AKA “Kartagener syndrome”

A
  • Dynein associated disease
  • respiratory tract infections; male infertility
  • dynein is mislocalized in the cell and does not make it to the cilia
28
Q

Cause of Primary ciliary dyskinesia (PCD)

AKA “Kartagener syndrome”

A
  • mutation in the outer arm ciliary dynein heavy chain leads to:
    • dynein outer arms in cilia are missing
    • cilia are immotile
    • chronic infection of the respiratory tract
    • males sterile
29
Q

What is the rate-limiting step in cytoskeletal motor function?

A
  • product release following hydrolysis
    • a phosphate for myosin and kinesin
  • Binding to actin or microtubules accelerates the rate-limiting step.
30
Q

How do cytoskeletal motors work?

A
  • All convert the energy of ATP hydrolysis into mechanical work and heat.
  • Binding and/or hydrolysis of ATP causes conformational change in the motor.
31
Q

What can lead to rigor mortis in muscle?

A
  • depletion of ATP, which causes myosin to remain attached to muscle
32
Q

What determines the speed of myosin moving on an actin filament?

A
  • rate of myosin ATPase and Pi release
33
Q

Steps in myosin II moving down an actin filament:

A
  1. ATP binds and causes release of myosin motor from actin
  2. recovery stroke occurs
  3. ATP hydrolyzed
  4. myosin re-binds to actin
  5. phosphate from ATP hydrolysis released
  6. power stroke
  7. repeat
34
Q

Where/when can you regulate myosin II function?

A
  • at the kinetic step when ATP is hydrolyzed
  • at the step when a phosphate from ATP hydrolysis is released
35
Q

What causes strong binding of myosin II to actin, which ultimately leads to the power stroke?

A
  • release of the phosphate residue from ATP hydrolysis
36
Q

How does the kinesin motor function?

A

Same as myosin:

  1. Binding of ATP weakens affinity of kinesin for microtubule.
  2. After ATP hydrolysis, kinesin binds with higher affinity to microtubule.
  3. Binding to microtubule accelerates product release and conversion from weak to strong binding.
  4. Power stroke occurs.
37
Q

Does kinesin bind to alpha or beta tubulin?

A

beta tubulin in the microtubules

38
Q

Myosin substrate, filament, and direction of movement:

A
  • ATP
  • actin
  • plus-end (mostly)
39
Q

Kinesin substrate, filament, and direction of movement:

A
  • ATP
  • microtubules
  • plus-end (mostly)
40
Q

Dynein substrate, filament, and direction of movement:

A
  • ATP
  • microtubules
  • minus end
41
Q

What determines the localization of a cytoskeletal motor?

A

the tail region of the motor

42
Q

Melanin transport:

A
  • melanin produced by melanocytes
  • melanin placed in vesicles called melanosomes.
  • melanosomes transported on microtubules and actin filaments to the periphery of the cell where they are taken up by keratinocytes.

Myosin V is required for transport to the periphery.

43
Q

What myosin transports melanin from the melanocytes to the keratinocytes?

A

Myosin V

44
Q

Besides myosin V, what else is required to move melanin from the nucleus of a cell to the periphery?

A
  • myosin V tail binds melanophilin, which is bound to Rab27aGTP/melanin
45
Q

Griscelli type 1 and Elejalde syndromes:

A
  • due to mutations in myosin Va, melanophilin or Rab27a
  • patients have silvery hair, light skin in child of dark-skinned parents
  • severe neurological effects
    • melanin in skin is clumped in basal layer
    • melanin in hair is clumped in center

BMS2.15 Cytoskeleton 2 (2 decks)

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