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Year 1 - Biochemistry > 1.7 Sub-cellular organelles, 1.8 Nucleus and 1.9 Trafficking > Flashcards

1.7 Sub-cellular organelles, 1.8 Nucleus and 1.9 Trafficking Flashcards

1
Q

What are the functions of biological membranes?

A

Barrier
Selective permeability (i.e. to ions, maintains concentration gradient)
Response to external stimuli
Electrical excitability (allowed by selective permeability)
Energy conversion processes (through concentrating components)
Signalling to external environments

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2
Q
  • What is the typical volume of a mammalian cell?
A

4 fl (4 x10^-18l)

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3
Q
  • What is the composition of a typical mammalian cell?
A 
70% Water
18% Protein
3% Phospholipids
3% Small metabolite molecules
2% Lipids
2% Polysaccharides
1.1% RNA
1% Inorganic ions
0.25% DNA
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4
Q

What is the structure of a membrane?

A

Sheet-like and only a few molecules thick (50-70 angstroms, 5-7nm)
Contain proteins embedded in a phospholipid bilayer
Phospholipid bilayer is asymmetric, with phospholipids forming different patches of similarly composition phospholipids - this also varies between the outside and the inside of the bilayer (i.e. some phospholipids are inside-specific)

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5
Q

What are membranes?

A

Functional, self-repairing, closed boundaries/interfaces between 2 compartments

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6
Q

How are distinctive functions of the membrane mediated?

A

By membrane proteins

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7
Q

How do the two faces of a membrane differ for protein symmetry?

A

Absolute asymmetry, completely different

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8
Q

How do the two faces of a membrane differ for phospholipid symmetry?

A

Relative asymmetry, just different species of phospholipid present

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9
Q

What forces hold membranes together?

A

They are non-covalent assembles, using cooperative non-covalent forces to hold the membranes together

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10
Q

How fluid is a membrane?

A

Highly fluid - ‘a two-dimensional solution of orientated proteins and lipids’

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11
Q

What are lipid rafts?

A

Clusters of phospholipids that form patches of ‘rafts’ with distinct protein composition and properties

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12
Q

What two forms can a membrane take?

A

Crystal (more rigid, below a certain temperature, i.e. at 15 degrees)
Fluid (more mobile, above a certain temperature - designed to be fluid in our bodies, exists this way at a physiological temperature)

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13
Q

What are organelles?

A

These are internal membrane-bound compartments with specific functions that exist within eukaryotic cells. They mediate specific independent functions within the cell

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14
Q

How do different cell types vary when concerning organelles?

A

They differ in number, size and shape to reflect the functional needs of each cell type - this is very variable and highly regulated

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15
Q

What is the function of the nucleus?`

A

Store/repository of genetic information, site of selective retrieval programmes for differentiation (i.e. has some control over gene expression)

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16
Q

What is the function of mitochondria?

A

This is the site of energy conversions and lipid metabolism - involved in aerobic respiration

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17
Q

What is the function of the rough endoplasmic reticulum?

A

Synthesises proteins for export

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18
Q

What is the function of the smooth endoplasmic reticulum?

A

Produces, packages and modifies lipids e.g. steroid secretion

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19
Q

What is the function of the Golgi apparatus?

A

Known as the ‘cell’s post office’, involved in packaging, modifying and sorting proteins, preparing them for secretion, and the sorting and transporting of lipids. The Golgi apparatus is also involved in the production of vesicles, including specialised ones such as lysosomes.

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20
Q

What is the structure and function of the trans Golgi network?

A

This is a series of tubules on the face of the Golgi apparatus that connect the cisternae. The are the site of a major transport pathway that allows for the processing and transport of glycoproteins and glycoproteins

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21
Q

What are the secretory granules (or large dense-core vesicles, LDCVs)?

A

These are unique organelles that contain neuropeptides or hormones, which have been packaged and stored for secretion via the regulated secretory pathway (RSP), and will be released upon stimulation. Are found in neuroendocrine and endocrine cells.

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22
Q

What are the ERs, Golgi apparatus, trans Golgi network and secretory granules all involved in?

A

The secretory pathway

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23
Q

What is the function of endosomes/vesicles?

A

Heterogenous (not all the same/with the same contents) organelles that sort and deliver internalised material from the cell surface and allow for the transport of molecules from the Golgi apparatus to lysosomes or vacuoles.

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24
Q

What is the structure and function of phagosomes?

A

These are the vesicles formed around material digested by phagocytes, allowing the cell to break down potentially harmful foreign material into harmless components, acting as a vital part of the immune response.

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25
Q

What is the function of lysosomes?

A

The hydrolytic and acidic contents of these vesicles are important in digestion within the cell - faulty and old organelles are sent to the lysosomes to be broken down. They have also been shown to have a function during apoptosis/mediated cell death.
Intracellular digestion by acid hydrolases.

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26
Q

What is the structure of a nucleus?

A 
Has a nuclear envelope (porous double membrane)
Nucleolus (dense round body of chromatin within the nucleus, where ribosomal subunits are assembled)
Nuclear matrix (contains the genetic information and nuclear lamina)
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27
Q

What is the structure of mitochondria?

A

Double membraned organelle, with the inner membrane forming folds known as cristae. Contains its own DNA and ribosomes. Can be spherical or long. Readily stained by acidic dies (acidophilic).

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28
Q

What is the structure of rough endoplasmic reticulum?

A

Double membranes form sacs/membrane-limited channels known as cisternae, rough ER is studded with ribosomes to aid function. Also known as granular ER.

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29
Q

What is the structure of smooth endoplasmic reticulum?

A

Double membranes form sacs/membrane-limited channels known as cisternae, smooth ER doesn’t have any ribosomes present. Also known as agranular ER.

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30
Q

What is the structure of the Golgi apparatus?

A

Membrane-bound organelle that forms stacks of sacs known as cisternae. Often found near the rough ER and the nucleus. Vesicles are able to bud off of the Golgi apparatus, and it is constantly regenerating.

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31
Q

What is the structure of the endosomes/vesicles?

A

These are membrane bound sacs that transport specific molecules.

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32
Q

What is the structure of a lysosome?

A

Simple structure - lysosomes are a simple phospholipid bilayer membrane surrounding highly acidic and hydrolytic enzymes.

  • Primary structure: smaller vesicles
  • Secondary structure: larger vesicles
  • Terminal structure: become residual bodies after digestion is complete (vesicles that contain indigestible material that will either be stored within the cytosol indefinitely or excreted from the cell via exocytosis)
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33
Q

What is the structure of a phagosome?

A

This is a vesicle (i.e. a membrane bound organelle) that surrounds the material engulfed by the phagocyte.

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34
Q

What pathway are endosomes, phagosomes and lysosomes involved in?

A

The uptake pathway.

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35
Q

What are some examples of dynamic, membrane-free organelles?

A

Lipid droplets, stress granules and the nucleolus within the nucleus.

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36
Q

How can various pathways (i.e. uptake or secretory) be observed?

A

Through the use of GFP (green fluorescent protein)

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37
Q

What does the cytoskeleton consist of?

A

Several complex networks of protein filaments extending throughout the cytoplasm.

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38
Q

What are the three subunits that make up the cytoskeleton?

A

Microtubules, microfilaments and intermediate filaments.

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39
Q

What are microtubules?

A

Tubulin polymers that are relatively inflexible and roughly 20-25nm diameter

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40
Q

What are microfilaments?

A

Actin polymers that are used for transport. Only 3-6nm.

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41
Q

What are intermediate filaments?

A

Intermediate filament polymers that form a meshwork throughout the cell, excluding the nucleus. 10nm in diameter.

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42
Q
  • How do viruses affect microtubules?
A

Viruses depolymerise microtubules, as can be seen in post-infection investigations, and this causes all of the organelles to collapse around the nucleus.

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43
Q

What is the function of the cytoskeleton?

A

It organises internal cellular space by providing a scaffold for organelle attachment.
It also orchestrates intracellular transport by providing guidance and motor power within the cell for vesicle movement.
Through specific molecular attachments to the plasma membrane allows for the cell to change shape and move over a substrate, or to form multicellular arrays (very important in the formation of epithelial sheets).

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44
Q

How is transport and communication between organelles achieved?

A

Through highly specialised mechanisms to keep the organelles separate. The transport of molecules is achieved through topologically conservative vesicular transport.
Vesicular transport uses membrane budding to generate free transport vesicles that move between a donor compartment and an acceptor compartment.

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45
Q

Why is it necessary that vesicular transport is topologically conservative?

A

Because vesicular transport is designed to prevent loss of organelle identity, or the leakage of its contents into the cytoplasm.

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46
Q

How are components destined for transport sorted?

A

Through selective membrane composition and soluble contents.

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47
Q

How are continued vesicular transport pathways reset?

A

This is achieved through specific machinery, usually recycling vesicles (which move in the opposite direction along the cytoskeleton and require no energy).

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48
Q

How are reactions limited to specific areas/how is compartmentalisation achieved?

A

This is through selective delivery and retention of the enzymes required, leading to efficient, unidirectional ‘production lines’ for multiple sequential modifications of cargo proteins (modifications include activating glycosylation, proteolysis, sulphation and nitrosylation), allowing the contents/vesicle to be labelled and transferred to/recognised by the correct compartment of or region of the cell.

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49
Q
  • How can the knowledge of where specifically labelled proteins go within the cell be used by researchers?
A

It can be used to investigate the machinery that is used to regulate the modification of cargo proteins - these show high evolutionary conservation from yeast to human.
The location of differently modified proteins was found through ‘chase’ experiments and the use of radioactive markers to track movement.

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50
Q

What are some examples of coat proteins involved in vesicle budding?

A

Clathrin, COP-1 and COP-2

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51
Q

What are the function of coat proteins?

A

They polymerise in patches at membranes to define budding sites, linking adaptor proteins, transmembrane cargo receptors and scission machinery to release budded vesicles.

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52
Q
  • What are some examples of adaptor proteins involved in vesicle budding?
A

The tetramers AP-1 and AP-2

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53
Q
  • What are some examples of transmembrane cargo receptors involved in vesicle budding?
A

Sec-23 family of proteins

54
Q
  • What is an example of the scission machinery involved in vesicle budding?
A

The GTP-ase mechano-protein dynamin

55
Q
  • What is scission?
A

The breakage of a chemical bond

56
Q

What is required for productive net transport of cargo?

A

That the composition of the anterograde (forward) vesicle is different to that of the retrograde (backward). This relies upon differences in the luminal environment between the donor and acceptor compartments.

57
Q

What permits quality control of vesicles and their contents?

A

The ability of cargo to travel forward once it has lost all retention signals or once it has been recognised by cargo receptors.

58
Q
  • How can protein transport machinery be studied using viruses?
A

Through assays of viral protein transport between isolated cellular compartments - using radioactive samples and X-ray film, the location of each target protein can be discovered and recorded.
Classic paper by Balch and others in 1984 -> a donor compartment (i.e. a Golgi apparatus) would be infected with a virus, and then organelles - containing different machinery - would be mixed. The acceptor fraction would then contain viral genetic information from the infected donor, allowing specific machinery found in that compartment to be isolated and noted.

59
Q

How do proteins associate with membranes and where?

A

They associate with specific ‘rafts’ of phospholipids, and the presence of proteins on the membrane can affect their shape and structure, even in organelles.

60
Q

How can rigidity of a membrane effect function?

A

Membranes are intended to be fluid, so crystallisation or low temperatures which cause an increase in rigidity can inhibit function of the membrane.

61
Q

How is cargo selection mediated?

A

This is achieved by mediation through receptor proteins - vesicular transport is highly selective. If cargo is labelled using coloured proteins, no mixes of colours will be observed inside vesicles.

62
Q

How is compartmentalisation achieved?

A

Through a membrane barrier
Through composition of macromolecules/non-membrane bound organelles that are instead transient, allowing them to be rapid and reversible, largely affected by the environment. These are difficult to obtain via centrifugation, therefore resulting in their more recent discovery.

63
Q

What is phase separation?

A

This is the cell’s fastest response to stress. This is where RNA is compartmentalised and sequestered from ribosomes to halt protein synthesis. This can be easily reversed once the stress is removed.

64
Q

What is the risk of phase separation?

A

High concentrations of material can be toxic or cause aggregation and become toxic that way, which is detrimental to the cell.

65
Q

What are the two vesicular trafficking routes?

A

The inward (endocytic) and outward (exocytic) pathways.

66
Q

What is exocytosis?

A

This is where material - that has been produced, packaged and processed successfully by the ER and Golgi apparatus - is allowed to exit the cell as the vesicle transporting it fuses with the plasmalemma and expels its contents into the extracellular matrix or allows content from within the vesicle to become part of the membrane.
A similar pathway is also seen whilst transporting lysozymes to lysosomes.
This is an active process (requires ATP)

67
Q

What is receptor mediated endocytosis (RME)?

A

This is where vesicles are stimulated to bud at the plasmalemma by receptors binding to molecules such as hormones and creating invaginations into the plasmalemma. Clathrin coats these pits and is vital for their formation, and the invagination can then be cleaved by dynamin to form the intracellular vesicle/endosome, transporting the contained molecules elsewhere.

68
Q

What is constitutive secretion?

A

This is where proteins or other molecules are transported continuously out of the cell, regardless of external factors or signals.

69
Q

What is regulated secretion?

A

This is where the secretion of molecules is controlled/regulated by external factors - in response to a signal, the cell will secrete a large amount of the cargo.

70
Q

What is transcytosis?

A

This is where various macromolecules are transported directly across a cell - the cargo is captured at one side of the cell and then secreted at the other (transcytosis + across cell transport).

71
Q
  • What is a clinical example of failed quality control in vesicular transport?
A

Cystic fibrosis - a genetic condition that causes serious damage to the airways and lungs. Progressive lung damage is the main cause of death, eventually leaving transplant as the only possible option. Infections can be cured but the fibrosis/effect of thick mucus cannot yet be cured.

72
Q
  • What type of disorder is cystic fibrosis?
A

An autosomal recessive genetic disorder caused by defects in both genes coding for the cystic fibrosis transmembrane conductance regulator (CFTR).

73
Q
  • What are some of the main symptoms of cystic fibrosis?
A

The usual function of cystic fibrosis transmembrane conductance regulator (CFTR) is that it forms an ATP-dependant multiple membrane spanning anion channel - loss of function prevents reabsorption of luminal chloride into surrounding cells, leading to a water potential gradient into the extracellular space and dehydration of cells, as sodium reabsorption is also limited. Lumenal viscosity is increased - this viscous content prevents action of normal protective muco-ciliary clearance, leading to reduced lung function and repetitive pulmonary infection. This leads up to build up of scar tissue/fibrosis which will eventually result in the need for a lung transplant.
Similar ciliary defects result in loss of pancreatic digestive secretion (causing malnutrition due to a malabsorption syndrome - failure to absorb necessary fat-soluble vitamins (A, D and K) can lead to coagulation defects - and fibrosis + cyst formation in the pancreas) and may result in infertility in men due to an inability to allow sperm traffic through the vas deferens.

74
Q
  • What mutation causes cystic fibrosis?
A

There is a three nucleotide (3 bp) deletion causing a deltaF-508 mutation (most common) - this deletes a phenylalanine amino acid which then prevents to protein from folding properly, causing it to be disposed of by regulatory machinery in the rough ER. Therefore, almost none of these proteins are able to reach the cell membrane and symptoms occur.

75
Q
  • What is the new approach to treating cystic fibrosis and which drugs are used to achieve it?
A

New treatments are based on our knowledge of trafficking CFTR through the cell.
Potentiators: These increase the potency of the CFTRs available at the cell surface. Ivacaftor.
Correctors: These increase number and function of CFTR channels at the cell surface. Lumacaftor (overcomes ER folding defect to enhance delivery to the surface).
Combination: This approach combines the other two, both increasing number and enhancing function of CFTR channels in the plasmalemma. Two correctors used, elexacaftor and tezacaftor, and one potentiator is used, ivacaftor.

76
Q

What is the approximate size of a cell nucleus?

A

5-10 micrometers

77
Q

What is the approximate size of a cell body?

A

20-30 micrometers

78
Q

What is the size of a red blood cell and why is this useful?

A

7 micrometers, this is useful as it can be used as a reference in microscopic slides as known size

79
Q

Are membranes specialised?

A

Yes - they can aid with the polarity of the cell, having specialisations depending on whether it is the apical, basal or lateral aspects of the cell.

80
Q

How are the nuclear membrane, endoplasmic reticulum and Golgi apparatus linked?

A

The nuclear membrane is continuous with the endoplasmic reticulum, which buds to the Golgi, which will then bud to the plasma membrane and endosomes. Works from the inside to the outside.

81
Q

What are autophagosomes?

A

Lysosomes that recycle bits of the cell that are no longer in use

82
Q

What are heterophagosomes?

A

Lysosomes that deal with/digest material brought into the cell

83
Q

What are proteasomes?

A

4 stacked rings (of proteins) that contain proteases in a central pore. Break down unwanted misfolded cytoplasmic proteins via proteolysis, present in the cytosol and the nucleus.

84
Q

How are proteins tagged for breakdown?

A

Through tagging with ubiquitin

85
Q

How can variation occur in tissues?

A
  • Position and ratio of tissues
  • In cells during cell cycle (cell division, periods between division/interphase)
  • In cell shape (ratio of nucleus:cytoplasm)
86
Q

Who, when and how was the nucleus discovered?

A

By Brown in 1833, as he investigated the epidermis of orchids via microscopy, finding a regular opaque spot in cells which he named the nucleus

87
Q

What colour does the nucleus stain when using H&E staining in light microscopy?

A

Nuclei stain a dark purple/brown

88
Q

What nuclear structures are possible to be viewed under transmission electron microscopy?

A
  • Nuclear membrane/envelope
  • Nuclear matrix
  • Chromatin
  • Nucleolus
89
Q

Are the chromosomes able to be viewed through microscopy?

A

Only during mitosis or meiosis

90
Q

What are the two types of chromatin present in interphase nuclei?

A

Euchromatin and heterochromatin

91
Q

What is heterochromatin?

A

Very dense regions of the genome containing mostly silenced genes/genes that don’t need to be expressed within this cell. Stains darkly due to dense structure.

92
Q

What is euchromatin?

A

Less dense/more open regions of the genome containing the genes that are frequently expressed. Due to more finely dispersed structure, stains more lightly.

93
Q

What is the nucleolus?

A

Region within the nucleus that contains regions of the genome that synthesise rRNA, controls ribosome production - the two sub-units are synthesised separately and then secreted out of the nucleus, ribosomes are key intermediaries in protein synthesis.

94
Q

How are ribosomes produced?

A

Ribosomal proteins enter the nucleus and nucleolus from outside the cell and then associate with the 4 rRNA strands (synthesised within the nucleolus) that give the ribosome its catalytic properties, allowing function. Ribosome is therefore assembled and synthesised in part within the nucleolus.

95
Q

What is the function of a nuclear pore?

A
  • Allows communication between cytoplasm and nucleus, both ways
  • Histones will go IN
96
Q

What are nuclear pores?

A

Holes in the nuclear envelope that are lined with proteins which regulate what goes in and out of the cell. They have a circular profile.

97
Q

What comes out of the nucleus and what goes in?

A

Out: mRNA and other functional RNA molecules, ribosomes will also exit.
In: Any proteins necessary for gene transcription (spliceosomes, various enzymes), activated transcription factors, ribosomal proteins (before assembly), histones

98
Q
  • What is some experimental evidence for the existence of nuclear pores?
A

Seen using both scanning and transmission EM, shown to have 8 fold symmetry and ‘flower petals’ structure.
Studied with more sophisticated image processing by Unwin and Milligan in 1982 - more detail revealed (80 nm across, rings, spokes, a central hub, large cytoplasmic particles, cylindrical shape, spokes attach it to the membrane).
Later, others studied pores using protein analysis, showing around 30 components.

99
Q

What defines the eukaryotic cells?

A

The nuclear membrane

100
Q

What is a Barr body?

A

An inactive X chromosome within a female cell (would be fatal in male cells). This occurs due to X inactivation.

101
Q

What is facultative heterochromatin?

A

Regions of chromatin that are reversibly silenced, only becoming inactivated in certain cell and tissues. Will contain genes with the potential for expression during certain stages in development, so is not a permanent feature of each cell in some cell types. This type of heterochromatin is what causes X chromosome inactivation in female somatic cells. Does not contain polymorphism unless genes contained within are mutated.

102
Q

What is constitutive heterochromatin?

A

Regions of the chromosomes that are permanently heterochromatic, containing highly repeated sequences of DNA/satellite DNA. Mostly structural in function - make up the centromeres and the telomeres of a chromosome. Is stable and a permanent feature of each cell type. Unlike facultative, can contain polymorphism/structure and sequence can vary between different cells.

103
Q

Why does a cell need a skeleton?

A
  • Cell motility
  • Cellular organisation (e.g. move organelles around a cell or vesicle transport for secretion)
  • Provides mechanical strength
104
Q

What are the three main protein filaments that make up the cytoskeleton?

A
  • Microfilaments
  • Microtubules
  • Intermediate filaments
105
Q

What are the features of microfilaments?

A
  • Actin (structural protein)
  • Determines cell shape
  • Allows cell movement
  • 5-7nm in diameter
106
Q

What are the features of microtubules?

A
  • Tubulin
  • Position organelles within the cell (‘railroad’)
  • Direct movement of intracellular transport
  • 25nm in diameter
107
Q

What are the features of intermediate filaments?

A
  • Large family of proteins (intermediate filament proteins), e.g. keratin
  • Provides mechanical strength and structure
  • 10-12nm in diameter
  • Amount and type varies between cells and their specific functions
108
Q
  • What sort of structure are actin filaments?
A
  • Double stranded helical polymers
  • Alpha form in muscle, beta and gamma in other cells
  • Form linear bundles, 2D and 3D networks throughout the cell
  • Concentrated just beneath plasma membrane
109
Q

Do microfilaments/actin filaments show polarity?

A

Yes, they have plus and minus ends:

  • Plus end, growth and shrinkage are fast
  • Minus end, growth and shrinkage are slow

Actin is constantly broken down and reformed in response to stimuli, no central area from which they radiate, subunits are spread throughout the cell

110
Q

How do microfilaments/actin filaments allow cells to move?

A
  • Rapid interchange between small soluble units and large filamentous polymer allows cells to respond fairly rapidly to stimuli, this process is ATP dependant
  • Filaments can be dissembled rapidly, soluble monomers diffuse to the stimulus and are then rapidly assembled at new site
  • This sort of response is seen in neutrophils when hunting bacteria or in growth cone extensions of axons, allowing them to be highly dynamic and respond to stimuli in the surrounding environment
  • Different type is used in muscles, aids in contraction
111
Q
  • What sort of structure do microtubules have?
A
  • Long, hollow cylinders made of proteins alpha and beta tubulin, form heterodimers
  • Rigid and straight, unlike actin filaments
  • Control direct movement of intracellular transport (organelles, vesicles, chromosomes)
112
Q

What is the MTOC?

A

The MicroTubule Organising Centre, where microtubules will radiate out from (centrosome, near nucleus, is usually the only one in animals)
- Stable minus ends are embedded into the MTOC

113
Q

Do microtubules/tubulin polymers show polarity?

A
  • Yes, microtubules grow faster at the plus end (distal from the MTOC)
  • Polymerisation is followed by nucleoside hydrolysis
  • Plus-side addition is fast, so hydrolysis can’t keep up/lags behind
  • Minus-side addition is slow so hydrolysis is able to catch up
114
Q

What is the ‘dynamic instability’ of microtubules?

A

Convert between shrinking and growing
- GTP favours growth
- GDP favours shrinking
Dynamic plus end is free in cytoplasm, experiencing growth and shrinkage

115
Q

What molecule is needed for the transport of organelles along microtubules?

A

ATP

116
Q

What is the function of kinesin motors/proteins?

A

They move organelles/cargo towards the plus end

Moves OUTWARD

117
Q

What is the function of dynein motors/proteins?

A

They move organelles/cargo towards the minus end

Moves INWARD

118
Q

In what direction can molecules move along microtubules?

A

Both ways - can be unidirectional or bidirectional

119
Q

How are microtubules different between fibroblasts and nerve cells?

A
  • In fibroblasts, all microtubules head out from the MTOC
  • In neurons, microtubule plus ends are at the synapse, minus ends are in the cell bodies (can be up to 1m long)
  • If transport down the axons fails/degeneration occurs, axon terminals will be starved
  • Vesicles will be transported along the microtubules at the synapse
  • In fibroblasts, vesicles are able to transport freely around the cell from one compartment to another
120
Q
  • What causes lissencephaly?
A

A mutation in alpha tubulin, defective neuronal migration during development results in areas of the brain appearing ‘smooth’/appearing without the characteristic gyri (‘folds’) that are normally present. Results in developmental issues

121
Q

What are MAPs?

A

Microtubule Associated Proteins e.g. MAP2 and MAP-tau (MAPT)
These bind to and stabilise microtubules, enhancing stability and resulting in longer microtubules - important for development (neural plasticity and neuronal stability)
Aggregates have been seen in Alzheimer’s disease

122
Q

What cell cycle process do microtubules aid?

A

Cell division (M phase), microtubules attach to the centromere during metaphase and draw apart sister chromatids during anaphase

123
Q

How do microtubules and dynein also allow mobility?

A

Seen in cilia and flagella as structures called ‘axonemes’, distinctive 9+2 structure at the core of cilia and flagella
Dynein walks along the adjacent microtubule to bend the axoneme

124
Q
  • What syndrome is caused by mutations in ciliary dynein?
A

Kartagener’s syndrome, cilia don’t work causing infertility, lung infections and left/right asymmetry deficit (due to issues during development)

125
Q

What are some examples of intermediate filaments?

A
  • Keratin (hair and epithelia)
  • Desmin (muscles)
  • Neurofilaments (cytoplasm of neurons)
  • Nuclear lamin proteins (fibrous proteins in the nucleus)
126
Q

What structure are intermediate filaments?

A

Protein multimers twisted into rope-like filaments, providing mechanical stability and structure for the cell

127
Q

What are keratins?

A
  • Diverse type of intermediate filaments
  • 20 in epithelia (e.g. skin)
  • 10 more specific to hair and nails
  • Networks held together by disulphide bonds
  • Mutations in these cause skin blistering
128
Q

What are neurofilaments?

A
  • Light, medium and heavy varieties (NF-L, NF-M, NF-H)
  • NF proteins/intermediate filaments form cross-links to provide the axon with tensile strength
  • Expression affects both the structure and the function of the axon
  • Level of NF expression controls axon diameter (structure) and therefore rate of conduction (function)
129
Q

What are nuclear lamins?

A
  • Intermediate filaments, there are types A, B and C
  • Form the nuclear lamina (meshwork of intermediate filaments lining the inside of the inner nuclear membrane)
  • Determines the shape of the nucleus
  • Provides anchoring points for chromosomes and proteins of the nuclear pore complex
  • Ancestral intermediate filament, supposedly
130
Q
  • Which drugs target actin and tubulin formation and why?
A
  • Can be found in toxins of plants and fungi that are avoiding being eaten
  • Taxol is used to target dividing cells in breast cancer (prevents cell division through preventing microtubule action during mitosis, therefore preventing/limiting tumour growth)
  • Some are useful laboratory agents, halt processes so that they can be investigated

Actin specific:
- Phalloidin (binds and stabilises filaments)
- Cytochalasin (caps filament plus ends)
- Swinholide (severs filaments)
- Latrunculin (binds to subunits and prevents their polymerisation)
Microtubule specific:
- Taxol (binds and stabilises microtubules)
- Colchicene, colcemid (binds to subunits and prevents their polymerisation)
- Vinblastine, vincristine (binds to subunits and prevents their polymerisation)
- Nocodazole (binds to subunits and prevents their polymerisation), useful to stop microtubule transport

Year 1 - Biochemistry (8 decks)

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