Lecture 37 The Cytoskeleton And Cell Movement

Front 1

In general, what is the cyotskeleton?

Back 1

a complex network of interconnnected filaments and tubules that extends throughout the cytosol from the nucues to the inner surface of the plasma membrane

Front 2

In general, what roles does the cytoskeletion play?

Back 2

Cell movement and division, movment of organelles

Front 3

What are the three majors structural elements of the eukaryotic cytoskeleton

Back 3

microtubules, microfilaments, intermediate filamtes

Front 4

What subunit polymerizes to form microtubules

Back 4

tubulin

Front 5

what subunit polymerizes to form microfilaments

Back 5

actin

Front 6

What types of proteins are found in prokaryotic cytoskeletions

Back 6

actin like MreB, tubulin like FtsZ

Front 7

What are the two main types of microtubules and what do they do?

Back 7

cytoplasmic microtubules- maintain axons, maintain polarized shape, mitotic and meiotic spindles, spatial disposition and directional movement of vesicles and organelles
axonemal microtubules- found in specific subcellular structures associated with cellular movement like cilla and flagella, highly organized,

Front 8

What are protofilaments?

Back 8

longitudinal arrays of linear polymers that form microtubules. there are usually 13 protofilaments arrganed side by side aroung the hollow center of the tubule

Front 9

What are the heterodimers that form the protofilaments of microtububles made of

Back 9

alpha tubulin and beta tubulin, the heterodimer does not dissociate under normal conditions

Front 10

Describe the alpha/ beta tubulin monomers in terms of their three binding domains

Back 10

1. GTP binding domain at the N terminus, a dmaoin in the middle
2. Binding domain in the middle where the MT poision colchicine binds
3. domain at C terminus where MT associated proteins like MAPs bind

Front 11

what is microtubule nucleation?

Back 11

The aggregation of tubulin dimers into clusters called oligomers, these oligomers serve as bases from which new microtubules can grow

Front 12

What is microtubule elongation

Back 12

once an MT has been nucleated, elongation occurs as new subunits are added at either end

Front 13

What is the critical concentration in terms of microtubule growth

Back 13

the tubulin heterodimer concentration at which MT assembly is exactly balance with dissembly

Front 14

Which end of the MT grows the fastest? Why does it grow faster?

Back 14

the plus end grows faster than the minus end. the plus end grows faster because the critical concentration is lower

Front 15

What is MT tread-milling and how does it occur

Back 15

MT tread-milling occurs when subunits are being added to the plus end and simultaneously removed from the minus end. This occurs when the free tubulin concentration is higher than the critical concentration for the plus end but lower than the that for the minus end

Front 16

Colchicine, Vinblastine, vincristine, and nocodazole all inhibit MT formation. Why are these called antimitotic drugs?

Back 16

They disrupt the mitotic spindle of dividing cells blocking the further progress of mitosis

Front 17

Why is GTP needed for MT assembly

Back 17

the association of GDP bound tubulin heterodimers with each other is too weak to support polymerization but hydrolysis of GTP is not necessary for aseembly since MTs polymerize from tubulin heterodimers boudn to a nonhydrolyzable anatogue of GTP

Front 18

What is the significance of the GTP cap on the plus end of microtubules

Back 18

Growing microtubules have GTP bound to their plus ends while shrinking MTs have GDP instead.The GTP cap provides a stable MT tip to which further dimers can be added. Hydrolysis of GTP by Beta tubulin eventually results in an unstable tip and depolymerization can occur rapidly.

Front 19

How is the frequency of catastrophe related to the cocentration of free tubulin?

Back 19

The frequency of catastrophe is inversely related to the free tubulin concentration. High tubulin concentrations make catastrophe less likely. At any tubulin concentration, catastrophe is more likely at the plus end of an MT (dynamic instability is more pronounced at the plus end)

Front 20

Where do microtubules commonly origintae from. Give an example.

Back 20

Microtubules commonly originate from a microtubule organizing center (MTOC). an example would be the centrosome

Front 21

Describe MT polarity in relationship to the MTOC

Back 21

MTs extend out from the MTOC to the periphery of the cell the minus ends are anchored in the MTOC and the plus ends extend out toward the cell membrane

Front 22

What are MAPs

Back 22

microtubule associated proteins, they bind to MTs along their allows and allow interaction with other filaments and cellular structures

Front 23

What is the role of gamma tubulin

Back 23

Gamma tubulin rings are found at the base of MTs that emerge from the centrosome. They serve to nucleate the assembly of new MTs away from the centrosome. in the absence of gamma tubulin ring complexes (gamma TuRC) centrosomes can no longer nucleate MTs

Front 24

What are + tip proteins

Back 24

MTs are generally too unstable to remain intact for a long time. Tip proteins stabilize MTs by capturing and protecting their growing plus ends. The directly or indirectly decreased the likely hood of catastrophe

Front 25

What are catastrophins

Back 25

proteins that promote the depolymeriztation of MTs

Front 26

What are several important functions of microfilaments

Back 26

contractile fibrils of muscle cells, locomotion, structural functions

Front 27

What proteins are the building block os microfilaments?

Back 27

actin

Front 28

What is the difference between G actin and G actin

Back 28

Individual actin molecules are G actin. G actin molecules polymerize to form microfilaments and are then referred to as F actin

Front 29

What are the two major groups of actin and what do they do?

Back 29

alpha actin- muscle specific
beta and gamma actin- nonmuscle actin,localize to different regions of the cell and interact with actin binding proteins

Front 30

Myosin subfragment 1 can be used to demonstrate actin polarity by giving a distinct arrowhead pattern. Which end is which? How does this polairty effect the addition and loss of G actin

Back 30

the pointed end is the minus end and the barbed end is the plus end. G actin is added and lost more quickly the plus end and added and lost more slowly at the minus end

Front 31

Which end of a growing microfilamnet will have ATP F actin

Back 31

the growing end will have ATP F actin because as g actin monomers are added to an MF the ATP bound to them is slowly hydrolyzed to ADP, ATP hydrolysis is not a strict requirement for MF elongation

Front 32

Describe how proteins regulate actin polymerization

Back 32

The growth of microfilaments depends on the concentration of ATP bound G actin. In a cell, free G actin ib bound by thymosin B4. Proflin transfers G actin monomers from the thymosin B4 complex to the end of a growing filament.

Front 33

Describe the role of capping proteins in actin polymerization

Back 33

Capping proteins bind the end of a filament and prevent further addition or loss of subunits thereby stabilizing it

Front 34

Describe actin corsslinking

Back 34

Actin networks can form from crosslinked MFs. Filamin is a protein that can as as "splicers" and join two MFs together

Front 35

List some things that actin interacting proteins do

Back 35

regulate polymerization, cap actin filaments, crosslink actin filaments, sever actin filaments, bundle actin into filaments, link actin to membranes, promote growth and branching

Front 36

Describe an actin dendritic network and how they are formed

Back 36

They are branched networks of actin that are a feature of lamellipodia in migrating cells. The Arp2/3 complex helps branches form by nucleating new branches on the sides of existing filaments. Arp2/3 is activated by WASP

Front 37

how are inositol phospholipids involved with actin

Back 37

They are a type of membrane phospholipid that regulates actin assembly. PIP2 can bind to profilin, CapZ, and ezrin and is though to regulate the ability of these proteins to interact with actin

Front 38

How are Rho family GTPases involved with actin regulation

Back 38

The cytoskeleton resonds to growth factors. These signals affect the cytoskeletion by acting on G proteins like Rac, Rho, and Cdc42 which regulate actin polymerization and cell protrusions. these proteins can also activate WASP which continues on to activate the Arp2/3 complex leading to actin branching

Front 39

Briefly describe intermeidiate filaments

Back 39

they are the most stable and least soluble constituents of the cytoskeletion, they serve as a scaffold to support the entire cytoskeletal framework, they do not appear to be polarized. they are also tissue specific

Front 40

WHat is the basic subunit of an intermediate filament

Back 40

two IF polypeptides intertwined into a coiled coil

Front 41

Describe intermediate filament assembly

Back 41

Two IF polypeptides form a coiled coil. The two dimers then form a tetrameric protofilament. The protofilaments interact with each other and form the intermediate filament

Front 42

What does neurite outgrowth depend on

Back 42

bounded actin filaments (as regulated by Ena/VASP which is similar to WASP Arp2/3) and dynamic microtubules