Cytoskeleton Flashcards

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1
Q

Why does a cell need a cytoskeleton?

A

To keep its shape and modify it in response to environmental cues

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2
Q

What in cells needs to be organised by the cytoskeleton?

A

Cells contain proteins organised in filamentous structures involved in:
- establishing cell shape
- providing mechanical strength
- cell movement
- chromosome separation
- intracellular transport of organelles

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3
Q

How is the cytoskeleton structured?

A
  • it is constituted of filamentous structures
  • there are 3 types:
    1. Actin filaments (microfilaments)
    2. Intermediate filaments
    3. Microtubules
  • also uses a large number of accessory proteins to maintain and regulate the properties associated with the filaments
  • each type of filament has distinct mechanical properties and dynamics, but certain fundamental properties are common
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4
Q

What are the cytoskeleton’s accessory proteins?

A
  1. cytoskeleton binding proteins
  2. cytoskeleton association proteins
  3. motor proteins
    They regulate:
    - site/rate of filament formation (nucleation)
    - polymerisation or depolymerisation
    - function
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5
Q

What level of deformation do the 3 filaments exhibit?

A
  • actin = low level with a medium force
  • intermediate = very high level with a high force
  • microtubules = high level with a very low force
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6
Q

What are the protein subunits for each filament?

A
  • actin = actin monomer
  • intermediate = various proteins with an alpha helical coiled coil
  • microtubule = tubulin heterodimer
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7
Q

What is the bound nucleotide for each filament?

A
  • actin = ATP
  • intermediate = none
  • microtubules = GTP
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8
Q

What is the dynamic instability of each filament?

A
  • actin = no
  • intermediate = no
  • microtubules = yes
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9
Q

Is the cytoskeleton dynamic?

A
  • it is dynamic and is facilitated by its organisation
  • this contains polymers made from monomers which are very abundant and aren’t covalently linked
  • this does not mean it is chaotic
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10
Q

What are intermediate filaments?

A
  • present in nearly all animals but absent from plants and fungi
  • rope like network of filaments in the cell
  • main function is maintenance of cell structure by providing tensile strength to the cell
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11
Q

What is the structure of an intermediate filament?

A
  • starts with an alpha-helical region monomer
  • two of these coil together to form a coiled-coil dimer
  • two of these come together to form a staggered tetramer
  • eight tetramers twist together to form the filament
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12
Q

How do intermediate filaments differ from actin and microtubules?

A
  • do not have a defined polarity (no +/- ends)
  • do not have associated motor proteins
  • do not bind to nucleotides (ATP/GTP)
  • very stable compared
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13
Q

How is tissue specific expression of IF proteins useful for diagnostics?

A
  • IF gene expression is often unaffected
  • cancer cells lose the characteristic shape of the parent tissue
  • identification of IF proteins in tumour biopsies using antibodies can pinpoint origin of tumours (eg neurofilaments in metastatic cells from brain cancer)
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14
Q

What are the 4 type of IF proteins?

A
  1. Keratins - in epithelia
  2. Vimentin - in connective tissue, muscle cells, neuroglial cells
  3. Neurofilaments - in nerve cells
  4. Nuclear lamins - in all animal cells
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15
Q

What is the function of the IF proteins?

A

provide tensile strength in the cytoplasm which allows cells to withstand mechanical stress (and stretch)

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16
Q

What is the function of keratin?

A
  • found in stratified squamous epithelium
  • stem cells in the interior
  • dead cells at outermost surface
  • keratin remains - hard, waterproof resists abrasions
  • makes up hair, nails, skin, feathers
  • keratin forms a strong network through indirectly linking to neighbouring cells
  • disruption of this results in blistering
17
Q

What do hemidesmosomes do?

A
  • mediate cell matrix adhesion between epithelial cells and basal lamina
  • integrins alpha6beta4 binds to proteins in the plaques and to laminin in the extracellular matrix
18
Q

What is the function of vimentin?

A
  • present in connective tissue and muscles
  • require trans-epithelial migration (ability of WBCs to leave blood to combat infection)
  • process is impaired in vimentin mutant mice
19
Q

What is the function of desmin?

A
  • tethered to the Z disk
  • develop the sacromere
  • do not participate in contraction but maintain structural integrity
  • mutant mice have misaligned muscle fibres
  • mutations in human desmin causes muscle disorders
20
Q

What is the function of neurofilaments?

A
  • present in neurons
  • important for nervous system function
  • unlike other IF, they have side arms that project from the core filament
  • fill and pack the cytoplasm of neurons
  • neurons in KO mice make axons with smaller diameters
  • Charcot-Marie-Tooth disease = neuropathy where peripheral nervous system degenerates
21
Q

What are the functions of the IFs in the nucleus?

A
  • present in all nucleated eukaryotic cells
  • form mesh rather than rope like structure
  • line in the inner face of the nuclear envelope to strengthen it and to provide attachment sites for chromatin
  • disassemble and reform at each cell division as nuclear envelope disintegrates
22
Q

What is the function of nuclear lamins?

A
  • present in the nuclei of all cells
  • form a basket like structure on inner side of nuclear membrane that protects the structure of the nucleus
  • disassemble when cells enter mitosis
23
Q

What are the IF binding proteins (IFBPs)?

A
  • mainly linkers of IF structures
  • stabilise and reinforce IFs into 3D networks
  • examples:
    1. Fillagrin = binds keratin filaments into bundles
    2. Synamin and Plectin = bind desmin and vimentin, link IF to other cytoskeleton compounds (ie actin and microtubules) as well as to cell-cell contact structures (desmosomes)
    3. Plakins = keep the contact between desmosomes of epithelial cells
24
Q

What is the function of microtubules?

A
  • organised to perform specific functions
  • establish an internal polarity to movements and structures in the interphase cell
  • participate in chromosome segregation during cell division
  • establish cell polarity during cellular movement
  • produce extracellular movement via beating of cilia and flagella
25
Q

What is the structure of a microtubule?

A
  • alpha-tubulin and beta-tubulin join to form a tubulin heterodimer
  • many of these join in a linear structure to form a protofilament which has a + and a - end
  • the protofilament is structured so that there is a lumen down the middle
  • the subunit addition takes place predominantly at the + end
  • they have a cap of GTP at the + end
26
Q

Do microtubules exhibit dynamic instability?

A
  • the total mass of polymerised tubal in remains constant but individual microtubules are dynamic
  • growth = assembly of microtuble
  • shrinkage = disassembly of microtubule
  • catastrophe = switching from growth to shrinking
  • rescue = switching from shrinking to growth