Cytoskeleton Flashcards

(95 cards)

1
Q

What is the real version of the cell?

A

The cell is a complex system controlled on a sub-second time scale over sub- to thousands of microns

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2
Q

The cytoskeleton is…

A

The skeleton and muscles of cells

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3
Q

Define the cytoskeleton

A

A system of protein polymers that allow:

  1. architecture
  2. shape
  3. motility of cells
  4. directed movement of organelles and molecules in the cell
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4
Q

Components of the cytoskeleton

A

Microtubules
Microfilaments (actin filaments)
Intermediate filaments
Host of accessory and regulatory proteins

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5
Q

Polymers of tubulin dimers made up _____ and _____

A

Polymers of tubulin dimers made up alpha-tubulin and beta-tubulin

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6
Q

Tubulin is what kind of enzyme

A

A GTPase

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7
Q

Is tubulin solid or hollow and describe more

A

Hollow with outer diameter of 24 nm

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8
Q

What proteins stabilize and space the polymers and regulate interactions between cytoskeletal elements?

A

Accessory proteins called microtubule-associated proteins (MAPs)

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9
Q

What are properties of microtubules?

A

Highly dynamic if not stabilized (can undergo rapid bouts of assembly and disassembly)

Act as substrate for microtubule-based proteins to transport cargo (organelles)

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10
Q

Describe the structure of microtubules

A

Polarized polymer with a plus and minus end

Plus end = dynamic (lengthens and shortens)

Motor proteins read the polarity and go to one end or the other

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11
Q

Functions of microtubules are…

A
  1. Make up the mitotic spindle
  2. Provide railways for organelle transport in most interphase cells
  3. Key determinant of cell shape
  4. Important in neurons for cell shape and axonal transport
  5. Provide the backbone for cilia and flagella
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12
Q

How many protofilaments are microtubules made of?

A

13 (+_)

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13
Q

What are protofilaments?

A

Stacks of tubulin dimers

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14
Q

What end is dynein directed towards?

A

Minus end

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15
Q

What end is kinesin directed towards?

A

+ end

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16
Q

Microtubule Associated Proteins are

A

Structural non-motor proteins

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17
Q

What are the functions of MAPs?

A

Organize MTs

Regulate MTs stability

Regulate MT dynamics

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18
Q

What is nucleation?

A

Genesis of a cytoskeletal polymer

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19
Q

Polymerization

A

The elongation of a cytoskeletal polymer following the initial nucleation

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20
Q

Nucleation for MTs occurs where?

A

Centrosome

Recent research indicates that golgi fragments may also nucleate MTs

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21
Q

Gamma tubulin in centrosome is only required for what?

A

Nucleation

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22
Q

The basal body is what?

A

A microtubule organizing center for cilia and flagella

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23
Q

What is a 9+2 structure of cilia and flagella?

A

The axoneme

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24
Q

What drives axonemal motility?

A

Dynein

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25
Immotile Cilia Syndrome
A body-wide defect in axonemal structure that result in obstructive lung disease and sterile males
26
Kartagener's Syndrome
A combination of Situs inversus (reversal of normal body asymmetry) and Immotile Cilia Syndrome
27
Cancer
Target for therapeutics, e.g. disruption of MT dynamics to block cell division (e.g., Taxol)
28
Diseases associated with malfunction of microtubule based cellular structures
Immotile Cilia Syndrome Kartagener's syndrome Cancer Lissencephaly Charcot-Marie-Tooth disease type 2A Neurodegenerative disorders
29
Lissencephaly
Mutations in microtubule proteins LIS1 and doublecortin
30
Charcot-Marie-Tooth disease type 2A
Mutation in specific kinesin has been reported in one case
31
What occurs in neurodegenerative disorders related to cytoskeleton?
Abnormalities/mutations in tau, dynein, kinesin, spastin
32
What do neurotopic viruses do?
Exploit neuron's microtubule based transport system to reach cell bodies
33
Microfilaments are
Non-hollow polymers of the globular protein actin
34
Actin is what type of enzyme?
ATPase
35
What shape is actin?
Helical
36
Diameter of actin
Roughly 7 nm
37
Properties of actin
1. Highly dynamic if not stabilized; undergo rapid bouts of assembly and disassembly 2. Variety of configurations regulated by accessory proteins 3. Substrate for members of the myosin family of motors to transport cargo 4. Unlike microtubules, actin filaments don't have specific organizing centers like centrosome and can be nucleated almost anywhere in the cell
38
Structure of microfilaments (describe both ends)
Polarized filament with barbed end and pointed end
39
For actin which end is favoured for assembly?
Barbed end
40
Myosin and polarity of microfilaments
Myosin motors read the polarity and move toward one end or the other (most move toward + end)
41
Functions of microfilaments
1. Concentrated in cell cortex for various functions 2. Cleavage furrow for pinching off cells in final stages of mitosis 3. Cell motility 4. Short-range organelle transport 5. Contractility (in both muscle and non-muscle)
42
What are 3 actin isoforms?
Alpha, beta, and gamma
43
Alpha actin is _____ _____
Muscle specific
44
Beta and gamma are found in ___ ____
Most cells
45
For nucleation and polymerization, actin must be...
ATP loaded
46
Myosins
F-actin associated force generating mechanoenzymes with roles in contractility and intracellular transport
47
Most myosins move toward which end of filaments?
barbed end
48
Microvilli
Actin based epithelial projections
49
F-actin and myosin II are located at the ___ ___ during cell division
contractile ring
50
F-actin serves as ____ for spectrin web
scaffold
51
Diseases association with malfunction of actin based cellular structures
1. Hereditary spherocytosis 2. Hereditary elliptocytosis 3. Breast cancer 4. Familial hypertropic cardiomyopathy 5. Mutations in skeletal muscle actin
52
Hereditary spherocytosis
Deforms RBCs to fragile spherocytes bc of weakened binding affinity of spectrin to band 4.1
53
Hereditary elliptocytosis
Deforms red cells to fragile elliptocytes bc of incomplete formation of spectrin
54
Breast cancer
In some forms, actin associated protein Tensin, which links integrin receptors to actin cytoskeleton, is disrupted promoting metastatic migration of cancerous cells
55
Mutations in skeletal muscle actin
Associated with congenital myopathies characterized by structural abnormalities of the muscle and variable degrees of muscle weakness
56
Myosin VI mutations
Cause deafness
57
Myosin VII mutations
Associated with deafness, neurological disorder, and blindness
58
Pathogens take the endogenous actin machinery to...
Translocate within cells
59
Phalloidin from amanita phalloides (fungi)
Binds to and stabilizes actin filaments
60
Intermediate filaments structure
Non-polarized Roughly 10 nm in diameter Comparatively non-dynamic - much more stable
61
Functions of intermediate filaments
1. Space-filling elements 2. Give tensile strength 3. Specialized functions depending on cell type 4. Important at cell junctions
62
Intermediate filaments are much _____ _____ across cell types than microtubules or microfilaments
less conserved
63
Can different cells have different intermediate filaments? What can they be used for?
Yes and can be used as cell-specific "markers"
64
Diseases associated with malfunction of intermediate filament based cellular structures
1. Epidermolysis bullosa simplex 2. Progeria
65
Epidermolysis bullosa simplex
Mutation in keratin genes expressed in basal cell layer of epidermis, result in a skin that is very sensitive to mechanical injury
66
Progeria
'Fast aging disease' associated with a mutation in nuclear lamin protein
67
How many distinct diseases have been associated with the intermediate filament gene family?
76
68
Keratins are mutated in more than __ diseases
20
69
Desmin is mutated in _________
cardiomyopathies
70
Neurofilament proteins
Small subunit mutated in the IF/2E forms of Charcot-Marie Tooth Disease
71
Periphin
Induced after peripheral nerve injury
72
Glial Fibrillary Acidic Protein
Mutated in Alexander disease (leukodystrophy resulting in abnormal myelin)
73
Arp2/3 binds to...
Pre-existing filament
74
Describe parts of microvilli
1. Barbed end always found at tip 2. Actin filaments 3. Lateral arm (myosin I-calmodulin): myosin I used as structural protein 4. Villin fimbrin: make sure filaments are nicely arranged 5. Terminal web at bottom
75
Describe structures of Myosin I, II, and V
Myosin I: has calmodulin light chains (monomeric so only 1 heavy chain) Myosin II: has regulatory light chain and essential light chain (dimeric) Myosin V: has calmodulin light chains (dimeric)
76
Formins and Spire make what?
Individuals filaments - do not need prior filaments
77
Give 2 examples of pathogen using endogenous actin machinery to translocate within cells
Listeria monocytogenes infection Shigella flexneri infection
78
List 3 leading edge meshworks
Arp 2/3 Profilin Cofilin
79
List 3 stress fibers
Myosin Alpha-actinin Formins
80
Periphery actin filaments are nucleated by...
Arp2/3
81
Center of cell nucleated by...
Formins
82
The ability of cell to migrate is dependent on what?
Actin cytoskeleton
83
There is a physical link between the actin cytoskeleton and...
The extracellular environment
84
Describe kinesin structure
Light chains, heavy chains, coiled coil, and head domain
85
Describe dynein structure
Light, heavy, intermediate chains, and head domain
86
Give an example of a neurotopic virus
Herpes virus
87
What do light and intermediate chains of dynein do?
Regulate function & control what it's bound to
88
What are 2 MAPs?
Kinesin and dynein
89
Where is mucociliary escalator found?
Along airways
90
Dynein allows for what in MTs?
Allows MTs to bend by sliding them relative to one another
91
What does cancer drug Taxol do to MTs?
Binds MTs and stabilizes so they no longer have dynamic instability
92
Rabies virus binds dynein or kinesin?
Dynein when going to minus end where cell body is then goes on kinesin to go to nerve ending to release particles and cycle repeats
93
Why do myosin VI mutations cause deafness?
Prevent formation of the proper structure of stereocilia in inner ear
94
What is basic subunit of intermediate filament?
Tetramer
95