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Molecules to Medicine III > Cytoskeleton > Flashcards

Flashcards in Cytoskeleton Deck (62)
1

List at least 5 functions of the cytoskeleton

1. organize cells and their environment
2. cell shape
3. Mechanical strength
4. Structures of locomotion
5. Support of plasma membrane
6. Scaffold for spatial organization of organelles
7. Means of intracellular transport of organelles and other cargo

2

What are the physical properties of microtubules?

tubular (hollow-fiber)
up to many micro meters long
outer diameter of 25nm
flexible (but not resistant to stretching)

3

What are the functions of microtubules?

- Scaffolds for spatial organization of organelles in cell & cell movment
- Organelle movement
- Movement of cilia and flagella

(usually attached at one end to centrosome or Perinuclear Microtubule Organizing Center (MTOC))

4

What proteins form microtubules?

Alpha and beta tubulin

5

Can the GTP bound to the alpha tubulin hydrolyze?

No

6

Can the GTP bound to the beta tubulin hydrolyze?

Yes

7

Which end of the alpha-beta tubulin dimer is considered the positive end?

beta
- due to its capability to hydrolyze the GTP

8

What happens at the + end compared to the - end?

+ end tends to grow
- end tends to shrink

9

What is the tread-milling phenomenon?

Microtubule (MT) growth at the + end at the same rate as MT disassembly at the - end

10

What is dynamic instability?

Rapid shrinkage of MT from plus end until GTP containing dimers are added back (the GTP-rich cap)

11

How do MT capping proteins affect MT stability?

Increase it by protecting or adding GTP cap

12

Ho dow MT severing proteins affect MT stability?

Decrease it by exposing GDP rick parts
(ex. spastin, katanin)

13

What are centrioles?

- short cylinders at right angles to eachother
- divide and form mitotic spindle between them during mitosis
- bodies of cilia and flagella

14

Name 2 drugs that are known to modify MT polymerization dynamics

1. Colchicine (from crocus like flower) - inhibit MT polymerization
2. Vinblastine & Vincristine (madagascar periwinkle) - MT polymerization blockers
3. Paclitaxel (taxol from pacific yew tree) - binds and stabilizes MT's - tubule and tubulin aggregates

***interest in cancer treatment***

15

Explain the concept of molecular motors

the process whereby MT's used energy from ATP hydrolysis to move cargo along MT in a "walking motion" toward the + or - end (using a mechanochemical cycle)

16

Which direction does Kinesin take cargo?

Toward the plus end

17

What motor moves cargo towards the - end?

Dyneins

18

What are the 3 types of mitotic spindle MT's, and what do they do?

Astral MT:
radiate out from centrosomes

Kinetochore MT:
Attache to kinetochore from centromere of each duplicated chromosome

Overlap MT: interdigitate at the equator of the spindle

19

Which direction do the MT + ends face?

away from the centrosome

20

What are flagella?

Long MT's
Propel sperm by undulating motion

21

What are cilia?

shorter
occur in large numbers
on apical surface of various epithelial cells
Beat in whip like motion in wave like pattern=> move fluids over surface of cells (ex. Respiratory tract)

22

What are the functions of intermediate filaments

Provide intracellular mechanical support

23

What are the 2 categories of of IF's?

Cytoplasmic IF (including keratins, vimentins and neurofilament proteins)
Nuclear lamins

More heterogeneous than MTs

24

How do nuclear lamins provide support?

form a meshwork that stabilizes inner membrane of nuclear envelop and anchors chromosomes and nuclear pores

25

What is the structure of IFs?

elongated molecules
extended central alpha-helical domain
parallel coiled-coil of alpha helixes

Paired diamers associate antiparallel and form staggered tetramers

Tetramers participate in IF polymerization

8 tetramers assemble into protofilaments and pack together laterally to form 1 IF

=> at all levels: IF cross section contains 32individual alpha-helix coils

26

What is a unique property of IFs?

32 individual alpha-helix coils at each cross sectional area
=> high tensile strength

27

Where are IFs often located?

intercellular junctions

28

Name 2 types of IF proteins and where they are located

Vimentins - Majority of cell types

Keratins - dominant components of epidermis and its appendages

Neurofilament proteins - vertebrate axons (controls axonal diameter)

Gilial fibrillary acidic protein (GFAP) - astrocytes in CNS (important in inflamatory/ degenerative processes of brain)

29

What pathology can result from keratin mutations?

epidermolysis bullosa simplex
- epidermis highly sensitive to mechanical stress (blisters)
- related diseases affecting IFs that anchor filaments in desmosomes have similar symptoms

30

Name a pahtology related to neurofilaments

Charcot-marie-tooth syndrome
- change in axonal transport of neurofilament subunits
- causes peripheral neuropahty

ALS
-abnormal assembly

Progeria syndromes (various)
- mutation in lamin -> nucelar instability

31

What is a potential side effect of MT toxins used for chemotherapy?

peripheral neuropathy
- MT toxins block mytosis
- BUT also affect other MT functions like axoplasmic transport

32

What is a pathology associated with microtubule severing proteins?

Hereditary spastic paraplesia

33

What is G-actin?

Microfilament
- filamentous polymer of actin monomer
- ~7nm in diaeter

34

What induces G-actin to form F-actin?

presence of divalent cations and ATP

35

What are 4 important roles of actin?

muscle contraction
cell mobility
epithelial polarity
cell division

36

What are some of the actions of the accessory proteins that regulate actin?

60+ accessory proteins
- G- actin concentration (profilin)
- ADP to ATP exchange (profilin)
- Polymerization
- disassembly
- stabilize
- Crosslink
- sever (ADF/ Cofolin)
- cap (gelsolin)

37

What protein nucleates actin in a linear pattern?

Formin

38

What protein nucleates actin and causes it to branch?

Arp2/3

39

What is Rho

monomeric GTP activated by extracellular signal which induced actin polymerization

40

What is the role of actin at tight junctions?

It acts as an intracellular anchor to the tight strands forming the impenetrable cell junction
- connects cytoplasm of adjacent cells

41

What are adherens junctions?

protein complexes that occur at cell cell junctions between epithelial and endothelial cells
- more basal than tight junctions

42

What is actin's role in adherens junctions?

actin links cytoplasmic face of the junctions

43

What are microvilli

microscopic protrusions in cell membranes that increase surface area in order to maximize functions such as absorption, secretion, adhesion and mechanical transduction

44

How is actin related to microvilli?

A tight MF is the core of microvilli
- Actin bundles are held together by villin and fimbrin (cross linking proteins)
- actin bundles are linked laterally to plasma membrane by myosin-I

45

What is microvilli inclusion disease?

loss of microvilli

46

Describe myosin II (involved in muscle contraction)

Head region with ATPase activity and actin binding sites & tail region
- ATPase at + end
- tail binds to other molecules
- forms hetero-oligomers ( 2 heavy chains, 2 copies each of 2 light chains)
- combine to form thick filaments in muscle

47

Explain the power stroke between actin and myosin during muscle contraction

ATP binds myosin head where it is hydrolyzed by ATPase -> myosin is activated and goes into extended position (high energy)

Myosin head binds to exposed actin filament

Myosin releases ADP and phosphate -> returns to low E position (bringing actin with it)

ATP binds myosin head-> actin released -> cycle restarts

Contraction = hundreds of myosin heads in same direction at the same time

48

What is the function of myosin V?

cargo carrier to transport vessicles

49

What complex regulates lamelipodia formation?

Arp2/3

50

What complex regulates filopodia formation?

formins

51

How does actin induce cell movement using the lamellipodium?

polymerizes at + end to protrude lamellipodium -> unpolymerized actin moves toward plus end -> Myosin II causes contraction of - end

focal contacts contain integrins

52

What family of extra cellular molecules act to control actin organization and cell shape? What super family are they a part of?

Rho family
superfamily of Fas GTPases

53

When are Ras GTPases active v. inactive?

Active in GTP bound state
Inactive in GDP bound state

54

What is the role of Rho in relation to actin

causes formation of stress fibers & focal adhesions

55

What is the role of Rac activation?

formation of veils

56

What is the role of Cdc42?

protrusion of fillopodia

57

What is the role of actin in cell division?

actomyosin ring forms -> constricts -> forms clevage furrow -> separates the 2 daughter cells

highly regulated -> determine symmetry of daughter cells

58

What cells undergo asymmetric cell division?

erythroblast -> reticulcyte + macrophage

2n meakaryocyte -> 4n (abortive cytokenisis)-> up to 128n polyipolod megakaryocytic (abortive cytokenisis) -> platelets

spermatagonia -> sermatatid -> sperm + residual body

59

Give an example of cell motility in the context of development

migration of neural crest cells from extoderm adjacent to neural tube -> cover whole body as pigment cells

nerve fibers grow over long distances -> tipped by nerve growth cone (has ameboid movement)

60

Give an example of cell motility in the context of infection

polymorphonuclear leukocytes must exit blood vessels and migrate into tissues to reach infection site

As cancer cells become malignant they migrate and invade healthy tissues (metastasis) -> eventually establishing tumors in locations distant from origin

61

What is wiskott-aldrich syndrome? (WAS)

rare x linked immunodeficiency
- result of WASp mutations
SX: throbyocytopenia (low platelet # & size)
- recurrent infections

defective lamellipodia/ platelet formation
macrophages, neutrophil leukocytes are migration & chmotaxix deficient

62

What is lissencephaly?

Defect in brain development:
- no gyri -> smooth surface
- improper neuronal migration
- loss of function of n-cofilin
- severe mental retardation