DSA 4 Cytoskeleton

Question 1

Components of the cytoskeleton

Answer 1

filamentous proteins (microfilament (actin), microtubules, intermediate filments (not covered here

accessory proteins,

motor proteins, like myosins(actin motor protein), kinesins and dyneins (microtubule)

Question 2

characteristics of actin filaments (microfilaments)

Answer 2

most ubiquitous cytoskeletal protein in most cells is actin.

Polymerization of actin protein monomers(G-actin) creates thin ,flexible filaments (F-actin)

InF-actin, individualG-actin molecules are always oriented in the same direction relative to one another consequently, F-actin is polar. F-actin has two ends:

– Faster-growing “barbed end” (plus end).
– Slower-growing “pointed end” (minus end).

Question 3

fuction of microfilaments in cell

Answer 3

benneath the plasma membrane actin filaments make a newtwork that supports, shapes, allows cells to migrate, engulf particles and devide

Question 4

what are the actin associated proteins

Answer 4

Actin-binding proteins control actin filament polymerization, depolarization, and stability. Formin and the Arp2/3 complex are the main actin filament-initiation and elongation proteins

Formins: nucleate the actin monomer polymerization by binding ATP-actin. Moving down the developing filament, they add monomers to the plus end. Thus, formins is responsible for the linear unbranched actin filament initiation and elongation.

Arp2/3, drives the elongation of branching actin filaments, which are essential for cell migration/movement. The Arp2/3 proteins bind ATP- actin at filament plus ends to form a new branch. Once branching begins, Arp2/3 will remain at the branch base adjacent to the branch minus end. Mutation of WASp (protein association with Arp2/3) is associated with Wiscott-Aldrich syndrome/

Profilin- binds actin monomers and increases ADP-ATP exchange, increases ATP actin concentration

Question 5

what are the steps of Actin monomers polymerization

Answer 5

1. nucleation- 3 actins join
2. addition of actin on both sides : - end had ADP bound actin while the + end has ATP actin bound. then grows much faster at + end, but ATP not needed for growth but happens fater
3. Treadmiling (special to actin); when ATP actin added is equal to the ADP actin disassociating.

Question 6

Formins:

Answer 6

Formins: nucleate the actin monomer polymerization by binding ATP-actin. Moving down the developing filament, they add monomers to the plus end. Thus, formins is responsible for the linear unbranched actin filament initiation and elongation.

Question 7

Arp 2/3

Answer 7

drives the elongation of branching actin filaments, which are essential for cell migration/movement.

The Arp2/3 proteins bind ATP- actin at filament plus ends to form a new branch. Once branching begins, Arp2/3 will remain at the branch base adjacent to the branch minus end. Mutation of WASp (protein association with Arp2/3) is associated with Wiscott-Aldrich syndrome/

Question 8

Profilin

Answer 8

another actin-binding protein, binds actin monomers and increases ADP-ATP exchange. This boosts local ATP-actin concentration and actin polymerization.

Question 9

Wiscott-Aldrich Syndrome

muatation

Answer 9

Malepatientswithdefectsinproteinsthat activate the Arp2/3 complex, a protein of the Wiskott-Aldrich syndrome protein (WASP) family.

xlinked

Signsandsymptoms
– Recurrent respiratory infections (because
of hereditary immunodeficiency),
– Thrombocytopenia (low platelet count) present from birth on
– Eczema of the skin after the first month of life.

Question 10

________is another actin associated protein

in skeletal muscle

Answer 10

tropomyosin

in skeletal muscle

protect and stabalize actin

Question 11

________is another actin associated protein

for remodeling

Answer 11

cofilin can remodel or modify actin

generates new ends depol or pol after breaking the original

cell motility or division

Question 12

____ and _____ associated actin proteins that bind the membrane
structural bases

Answer 12

Spectrin (major contributor in RBC) and ankryn (anchor for spectrin

Question 13

defect in hereditary spherocytosis

affected individuals symptoms

Answer 13

RBCsare round (spherocytes) instead of concave. It results from
* Mutationsof ankyrin-1 ,resultinanankyrin-1protein
that does not bind the RBC membrane and is therefore
unavailable for spectrin binding.
* MutationsofSPTB(spectrinbeta)resultinaltered
spectrin that cannot associate correctly with actin in the RBC membrane.

anemia and jaundice

Question 14

_____ is another actin associated protein present in muscles

Answer 14

Dystrophin in muscles cellls

stabalizes sarcolemma

• It stabilizes the sarcolemma(plasma membrane of the muscle cell) during the stress of muscle contraction by maintaining a link between the cytoskeleton and the extracellular matrix.
• When dystrophinis absent, the sarcolemma is disrupted, allowing unregulated calcium entry, which causes necrosis of the muscle fiber.

Question 15

defect in Duchenne’s muscular dystrophy, an X- linked recessive condition.

and Becker

Answer 15

by A deficiency in dystrophin

X- linked recessive condition

Duchenne’s starts in early childhood – deletion with frameshift mutation

Becker slowly progressive -delition

Question 16

_____ are another actin related protein

what are the different types

Answer 16

myosins

Question 17

F-actin inhibitors

Answer 17

Cytochalasins

– Bind to the barded end preventing further addition of G-actin. – Produced by fungi

Phalloidin

– binds to F-actin preventing depolymerization.
– Produced by the Death cap mushroom Amanita phalloides.

Latrunculins

– disrupt F-actin by binding to G-actin and inducing directly F-actin depolymerization. – Derive from Red Sea sponge Lantrunculia magnifica

Question 18

microtubule structure and characteristics

Answer 18

heterodimers.
– α-tubulin bound to GTP
– β-tubulin bound to GTP

γ-tubulin is third type of tubulin which is concentrated in the centrosome, where it plays a critical role in initiating microtubule assembly

Polarized, with plus end which grows more rapidly than the minus end.

The tubulin subunits bind GTP

Unlike microfilaments undergo alternate phases of slow growth and rapid depolymerization i.e., dynamic instability.

Question 19

fuctions of microtubule

Answer 19

They function to determine cell shape and participate in a variety of cell movements, including some forms of cell locomotion, the intracellular transport of organelles, and the separation of chromosomes during mitosis.

Question 20

describe Polymerization of microtubules and dynamic instability

Answer 20

GTP binds to α- and β-tubulin, similar to ATP binding to actin, to regulate polymerization. Specifically, microtubule development involves adding GTP-bound tubulin dimers to the plus end.

GTP bound to β-tubulin (but not α-
tubulin) is hydrolyzed to GDP immediately after polymerization. GTP hydrolysis lowers tubulin dimer binding affinity, causing GDP-bound tubulin to dissociate from microtubule ends rapidly.

To prevent fast depolymerization, cells must anchor microtubule minus ends in the centrosome or microtubule organizing center.

Dynamic instability occurs when fast GTP hydrolysis at the plus end causes microtubules stabilized at the minus end to alternate between growth and shrinking

Question 21

what are the microtubule associated proteins (MAPs)? (5)

Answer 21

The microtubule organizing center (MTOC) or centrosome stabilizes microtubule minus ends in cilia and flagella

• Polymerases increase GTP-bound tubulin incorporation to promote growth.
• Depolymerases dissociates GTP-bound tubulin from the plus end, shrinking microtubules.
• Tau protein

-MAP2

-CAP

Question 22

What are the fuctions of

• Tau protein

-MAP2

-CAP

Answer 22

• Tau protein is a MAP protein stabilizes neuronal axon microtubules (tau protein is not present in dendrites) Modifications of tau protein including phosphorylation, acetylation, and ubiquitination has been associated with Alzheimer disease. Tau protein is specific to axonal microtubules.
• MAP2 is a MAP protein stabilizes neuronal dendritic microtubules. It functions similar to Tau in terms of stabilizing the microtubules.
• Cap proteins are MAPs that stabilizes both ends of dendritic and axonal microtubules because these microtubules are not connected to MOTC.

Question 23

microtubule targeting agents

Answer 23

Chochicine

vicristine and vinblastine

Maytansine

Taxol

(Coach May Taxis Vinyards)

Question 24

Coalchicine

Answer 24

inserts between the components of α/β- tubulin dimers and prevents its assembly into the plus end of microtubule.

Question 25

Vincristine and vinblastine

Answer 25

Vincristine and vinblastine occupy a space between adjacent α/β-tubulin heterodimers.

Question 26

Maytansine

Answer 26

Maytansine binds to β-tubulin at the plus end thus inhibiting filament prolongation.

Question 27

Taxol (ex. Paclitaxil)

Answer 27

binds to along microtubules to β-tubulin stabilizing them in polymerization state thus preventing their depolymerization.

Question 28

what proteins are responsible for carrying cargo in microtubules? and how do they work ?

Answer 28

Kinesin I and Dyneins (use ATP hydrolysis for energy of transportation)

Kinesin I: transports cargo towards the plus end (from center to periphery of cell) of microtubules, near the plasma membrane or cortex of cell
-transport NT along the aconal MT towards synaptic cleft

Dyneins: mediate transport towards the minus end of microtubules, facing the centrosome in the middle of cell (from periphery to the nucleus )

Question 29

viruses that use Dyneins to transport themselves into the cell’s cell body

Answer 29

Clostridium tetani, herpes simplex, poliovirus, rabies virus

rabi costa tetas por herpes

Question 30

centrosomes