Lecture 20 The Cytoskeleton I - Structure Flashcards

0
Q

Microtubules role

A
Slinky of life
Form tube like structure
determine the positions of membrane-enclosed organelles and direct the intracellular transport
Make up centrioles and mitotic spindle
Cilia and flagella
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1
Q

Actin Filaments roles

A

Like mardi-gras beads

Determine the shape of cell’s surface and are necessary for whole-cell locomotion, secretion, and endocytosis

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2
Q

Intermediate Filaments role

A

Like girders in building
Provide mechanical strength
Strong filament
resist mechanical stress

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3
Q

Accessory proteins role

A

Helps assemble

Dissemble and keep filaments togther

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4
Q

Actin characteristics

A
Color code: red
Two-stranded helical polymers of protein actin
Single globular form - G-acting
Filament form - F-actin
Flexible
5-9 diameters
Smallest
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5
Q

Microtubule characteristics

A

Color code: green
Made of tubulin subunits that are compact and globular
Long hollow cylinder
Straight
25 nm diameter
More rigid than actin filaments
Have one end attached to a single microtublule-organizing center called centrosomes
Bi-polar mitotic spindle to separate chromosomes

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6
Q

Intermediate filament characteristics

A

Color code: Blue
Rope(yarn)-like fiber
Diameter 10 nm
Large heterogeneous family
Smaller subunits that are elongated and fibrous (not globular)
Extend across the cytoplasm to provide mechanical strength
Span from one cell-cell junction to another to strengthen the epithelial sheet

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7
Q

What are protofilaments?

A

Long linear string of protein subunits joined end to end
Thermally unstable and easy to break
Cytoskeletal filaments are consisted of multiple protofilaments

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8
Q

Formation of cytoskeletal filament from multiple protofilaments bound side to side causes what?

A

A thermally stable structure: this requires breakage of several bonds in middle of stable filaments-resists breakage by ambient thermal conditions

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9
Q

What allows cytoskeleton to be more like yarn?

A

Staggered side to side binding of filaments allows filaments to tolerate bending and stretching forming yarn like structures (intermediate)

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10
Q

What is polymerization?

A

Assembly of actin or tubulin subunits into a linear polymer

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11
Q

what is depolymerization?

A

Removal of monomers at the ends of the polymer

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12
Q

For new large filament to form what must happen first?

A

Subunits must assemble into initial aggregate or nucleus: nucleation
There is a random collision of 3 subunits
-rate limiting step (lag phase)

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13
Q

What is tubulin?

A

Herterodimer of alpha-tubulin and beta-tubulin with non-covalent bonds
Both have a binding site for one GTP
GTP in the alpha-tubulin is never hydrolyzed
Longitudinal: alpha-beta
Lateral: Alpha-alpha or beta-beta
Beta are always at top

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14
Q

How are actin monomers arranged in actin filament?

A

Actin has a binding site for ATP or ADP
Arranged head-to-tail to generate structural polarity
Consists of 2 protofilaments, held by lateral contacts

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15
Q

Describe structural polarity

A

Plus end: fast-growing or shrinking end; has Beta-tubulin or referred as barbed end of actin filament

Minus end: slow-growing or shrinking end; has alpha-tubulin or the GTP-binding cleft on the actin monomer point towards to minus end, also referred as pointed end

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16
Q

Describe T and D form

A

T form: ATP/GTP bound

D form: ADP/GDP bound

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17
Q

When is ATP or GTP hydrolyzed to ADP or GDP?

A

Soon after the monomer assembles into the polymer

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18
Q

Describe treadmilling

A

Subunit addition at plus end is greater than at minus end
Plus end remains in T formation
Minus end adopts D formation
Subunits added at plus end and removed at minus end
The plus end grows while the minus end shrinks, called treadmilling
The polymer maintains a constant length

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19
Q

What does treadmilling predominate in?

A

Actin filaments

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20
Q

What is dynamic instability?

A

The rapid inter-conversion between a growing and shrinking state at a constant concentration of free subunits
Catastrophe and rescue

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21
Q

Castastrophe:

A

If nucleotide hydrolysis proceeds more rapidly than subunit addition, the cap is lost and the microtubule begins to shrink

In rapid growing microtubule, protofilaments containing GDP-subunits are forced into linear conformation by many lateral bonds, given a stable cap GTP-subunits

Loss of GTP cap allows the GDP-protofilaments to relax into the more curved conformation. This leads to a progressive disruption of the microtubule

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22
Q

Rescue:

A

GTP-containing subunits may still add to the shrinking end, and if enough add to form a cap, then the microtubule growth resumes

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23
Q

How are intermediate filaments constructed?

A

Each monomer is an elongated molecule with an extended central alpha helical domain
Monomer forms a parallel coiled-coil dimer with another monomer
A pair of dimers associates in an antiparallel manner to form a staggered tetramer
!!No nucleotide binding site and structural polarity!!

24
Q

What is formin?

A

Accessory proteins for actin subunits that nucleates assembly and remains associated with the growing plus end

25
Q

What is thymosin?

A

Accessory protein for actin subunits that binds to subunits and prevents assembly

26
Q

What is profilin?

A

Accessory protein for actin subunits that binds to subunits and speeds assembly

27
Q

What is ARP complex?

A

Accessory protein for actin subunits that nucleates assembly to form a web and remains associated with the minus end

28
Q

What is cofilin?

A

Accessory protein for actin filaments that binds ADP-actin filaments and accelerates disassembly

29
Q

What is gelsolin?

A

Accessory protein for actin filaments that severs actin filaments and binds to the plus end

30
Q

What is capping protein?

A

Accessory protein for actin filaments that prevents assembly and disassembly at plus end

31
Q

What is tropomyosin?

A

Accessory protein for actin filaments that stabilizes the filament

32
Q

What accessory proteins for actin filaments are involed with filament bundling, cross linking and attachment to membranes?

A

Fimbrin, alpha-actinin, filamin, spectrin,, ERM family

33
Q

MTOC

A

Microtubule-organizing center where microtubules are nucleated from a specific location

34
Q

What serves as a template that creates a microtubule with 13 protofilaments?

A

gamma-tubulin ring

35
Q

Alpha-actinin:

A

cross-links actin filaments into loose bundles, allowing myosin II to enter to make actin filaments contractile

36
Q

Fimbrin:

A

Cross-links actin filaments into tight bunles, excluding myosin II

37
Q

Filamin:

A

Promotes the formation of a loose and highly viscous gel-like network by clamping together 2 actin filaments roughly at right angles
Need this in order to extend membrane projections which help cells to crawl

38
Q

What does myosin, dyneins and kinesin all require?

A

Energy
They are motor proteins
Binding site in tail for cargo

Myosin - actin association
dyneins, kinesin - microtubules

Kinesin - plus end
Dyneins - minus end

39
Q

Filopodia:

A

Microspikes
Formed by migrating fibroblasts
One-dimensional
Contain a core of long, bundled actin filaments

40
Q

Lamellipodia

A

Formed by epithelial cells, fibroblasts and neurons
Two-dimensional, sheet-like structure
Contains cross-linked mesh of actin filaments, most lie in a plane parallel to the solid substratum

41
Q

What triggers global structural rearrangements in response to external signals?

A

A variety of cell-surface receptors

All external signals converge inside the cell on a monomeric GTPases: the Rho monomeric GTPase family

42
Q

Rho:

A

Act as molecular switches to control cell processes by cycling between an active, GTP-bound form and inactive, GDP-bound form

43
Q

What promotes actin polymerization at the cell periphery leading to the formation of Lamellipodia extensions?

A

Rac activation

44
Q

What triggers actin polymerization and bundling to form fliopodia?

A

Cdc42

45
Q

What promotes both the bundling of actin filaments with myosin II filaments into stress fibers and the clustering of integrins and associated proteins to form focal contacts?

A

Rho

46
Q

Where are microtubules primarily nucleated?

A

At the centrosome and this is mediated by gamma-tubulin

47
Q

Where are actin filaments nucleated near?

A

The plasma membrane and mediated by ARP complex and formin

48
Q

What happens during cell migration?

A

protrusion is formed at the leading edge by assembly of new actin filaments.
Newly protruded part adheres to the substratum, motor proteins (myosin II) generate contractile force to move cell body forward

49
Q

Staminin:

A

Tubulin dimers for microtubules that bind subunits, and prevents assembly

50
Q

gamma-TuRC:

A

Tubulin dimers - microtubules - that nucleates assembly and remains associated with minus end

51
Q

TIPS:

A

Tubulin dimers - microtubules - (plus end tracking proteins) remain associated with growing plus ends, and can link them to other structures

52
Q

Kinesin 13:

A

works on microtubules that enhances catastrophic disassembly at plus end

53
Q

Katanin:

A

Japanese word for “sword”

Severs microtubules

54
Q

MAPS:

A

Microtubule associated protein

stabilizes tubules by binding along sides

55
Q

XMAP215:

A

A microtubule associated protein that stabilizes plus ends and accelerates assembly

56
Q

Tau:

A

filament cross linking-(a MAP protein), MAP2: both cause bundling of microtubules

57
Q

Plectin:

A

cross-linking protein, links microtubules to intermediate filaments