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Biochemistry Muscoskeletal > Microtubules > Flashcards

Microtubules Flashcards

1
Q

General functions of microtubules

A

Transport

Org. Of organelles

Vesicle movement

Secreting proteins

Supporting structural proteins

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2
Q

The repeating monomers of mts

A

Alpha-beta tubulin

Alpha = will only bind GTP

Beta = can hydrolyze GTP —> GDP so it can bind both

Dimerization is spontaneous

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3
Q

Protofilament

A

Precursor…arrangement of linear repeats of alpha/beta dimers: its wrapped around in a hollow tube that has strong interactions

They align to form a microtubule ring

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4
Q

Polarity

A

(-) end = alpha-tubulin cap

(+) end = beta cap

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5
Q

Where do you see

Singlet? Doublets? Triplets?

A

Singlet = interphase, mitotic microtubules

Doublet = cilia and flagella (mt movement)

Triplet = structural mts…seen in basal bodies and centrioles

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6
Q

If you increase the concentration of the monomers —>

A

Dimer formation will increase

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7
Q

Once you hit the critical concentration

A

The dimer formation will level off…

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8
Q

The CC depends on what…

A

Whether or not you want to make mts…

You’ll get growth with appropriate concentration

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9
Q

Will the - or + side of the mt have a higher CC?

A

The - side will…therefore the assembly is more likely to occur at the + end and more rapidly

Think of the + end as the polymerizing end and - end ast the depolymerizing

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10
Q

Above the CC…GTP bound dimers are

A

Added creating a GTP cap that stabilize the positive end

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11
Q

Below the CC, the GTP will

A

Hydrolyze —> GDP…and create a GDP cap at the positive end

Which will become destabilized

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12
Q

Catastrophe

A

The unstable GDP cap formation and subsequent depolymerization

This can be relieved by adding GTP bound dimers

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13
Q
  1. If [heterodimer] < CC

Then?

A

MT depolymerizes

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14
Q

If [heterodimer] > CC

Then

A

MT polymerizes

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15
Q

CC+ < [heterodimer] < CC-

A

Treadmilling effect

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16
Q

What are the 2 conditions that affect the MT stability

A
  1. Dimer pool conc.

2. GTP/GDP status of beta-tubulin

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17
Q

MT stabilizing proteins (MAPs)

A

Has a (+) end that binds with the (-) charged MT

—> neutralizes it

This stabilizes the spatial arrangement of neighboring MTs

Has an acidic domain that maintains distance between neighboring MTs

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18
Q

Phosphorylation effect on MAPs

A

Adds (-) charge to inactivate MAP

—> destabilizes MTs

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19
Q

Kinesin-13

A

Bends +/- ends of MT into catastrophe and binds to dimers

Lowers [dimer] —> decrease polymerization

20
Q

Stathmin

A

Binds two dimers and bends similarly to kinesin

Enhances GTP —> GDP

Depolymerization

21
Q

Katanin

A

Breaking the MTs

This exposes GDP caps in the middle of MTs and creates several GDP caps —> catastrophe

Rapid degradation for (G2 —> mitosis transition) and (end of mitosis —> G1 transtion) to reorganize the cell

22
Q

Colchicine (drug)

A

Lowers [dimer] to below CC… by binding them

—> catastrophe

(Used to reduce WBCs migration in gout)

23
Q

Vinblastine (drug)

A

Destabilizing drug

Lung, breast, and teste cancers

24
Q

Podophyllotoxin (drug)

A

Destabilizing

Lung and genital tumors, genital warts

25
Q

Nocodazole

A

Prevents spindle assembly

Used in labs mainly

26
Q

Taxol

A

Stabilizing drug**

Inhibits mitosis

Breast and ovarian cancers

27
Q

Main cause of Alzheimers?

A

Hyperphosphorylation of MAPs

—> destabilizes the MTs

—> formation of tangles

28
Q

Role of Pin1 in Alzheimers treatment/prevention

A

Prevents the formation of the cisProline in the repeat sequence in the AB42 plaques and Tau tangles…

Makes it transProline —> prevents the phosphorylated state from being maintained (i.e. no hyperphosphorylation)

29
Q

MT org. Centers (MTOC) for…

  1. Interphase
  2. Mitosis
  3. Axon
  4. Cilia and flagella
A
  1. Centrosome
  2. Spindle poles
  3. MTOC
  4. Basal bodes
30
Q

Role of MTOCs

A

Anchor the (-) end of the MTs

Functions to start polymerization of MTs

31
Q

Kinesin motor proteins

A

Anterograde movements

Cargo (vesicles or organelles): (-) —> (+)

The kinesin tail binds to the cargo…

Two motor head domains bind to beta-tubulin…which walk along the MTs

Each step requires ATP hydrolysis

32
Q

Dynein motor proteins

A

Retrograde movement

Cargo (+) —> (-)

Tail of dyenin binds to cargo

Stalk binds to MTs

Head has ATPase…when hydrolyzes ATP —> head changes conformation —> results in movement of stalk = POWER STROKE

33
Q

Exocytosis

A

Glandular cells

Secretory vesicle moved using KINESIN

At the end of the MT…move along the actin cytoskeleton using the myosin motors to reach the plasma membrane and release its products

34
Q

Endocytosis

A

Endosomes are transported to their intracellular destination along MTs using

Dynein motor proteins

35
Q

Cilia and flagella use which motor proteins

A

Dynein (arms)

36
Q

Interphase (centrosome)

A

Centrosome is duplicated along with the DNA

37
Q

Mitotic MTs

A

Aster

Kinetochores

Polar

38
Q

Aster

A

Form spindle poles toward the cell cortex (away from metaphase plate)

Orient the spindle poles (MTOC/centrosome) to the axis on which the cell will divide

39
Q

Kinetochore

A

MTs

Attache spindle pole to centromere of chromosome

40
Q

Polar

A

MTs

Used in prometaphase and late anaphase (anaphase B)

As well as participating in orientation of the central spindle

41
Q

Prophase

A

Interphase MTs break down and are replaced by mitotic MTs and chromosomes condense

  1. Asters form
  2. Dynein proteins of aster —> move toward the (-) end of MTs —> pulling the spindle poles to the opposite sides of the nucleus
  3. .at the same time…kinesin motor proteins that are attached as cargo to a polar MT —> move toward the (+) end of the opposite polar MT

“Pushing forces in the overlap zone” + “pulling forces on asters” —> spindle poles moving apart

42
Q

Prometaphase

A

Nuclear envelope breaks down

Kinetochore MT and polar MTs are present and reach toward the central spindle region

Kinesin motor proteins move toward the (+) end of the MTs —> polar MTs push the duplicated centrosomes apart

43
Q

Metaphase

A

Chromosomes are aligned at the metaphase plate

In order for this to happen…the kinetochores need to treadmill

—> elongation = kinesin which holds onto the chromosome and amoves towards the (+) end of the MTs…this pushes the chromosome to center

—> shortening = kinesin-13 disassembles MT…and dynenin moves toward the (-) end of the MT …pulling the chromosome to the center

44
Q

Anaphase

A

Begins once all chromosomes are aligned at the palte

Cohesin = protein that holds the sister chromatids together at the cetromere breaks down…this allows the sisters to separate

45
Q

Anaphase A

A

Kinetochore MTs shorten and disassemble…pulls chromosomes to the poles

Done by kinesin-13 at both +/- ends

46
Q

Anaphase B

A

Polar MTs using kinesin motor proteins to move the two poles further apart (spindle pole separation)…bring the chromosomes with them…

Dynein of aster MTs move towards the (-) end of the aster MTs…

Togehter these processes result in the spindle pole separation and chromatid movement to the opposite sides of the cell

47
Q

Telophase

A

Nuclear envelope re-forms and a contractile ring made of myosin forms in the center…

Biochemistry Muscoskeletal (8 decks)

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