Microtubules Flashcards
Describe the functions of the cytoskeleton
- “Bones and muscles” of the cell: cell shape/polarity, cell motility, plasticity, segregation of chromosomes
- Railways of the cell: endocytosis, secretion, segregation of organelles, communication between organelles
Wht are the networks of intracellular filaments?
- Microtubules: centrosome, MTOC
- Actin filaments (microfilaments): lamellipodim, stress fibre
- Intermediate filaments: nuclear lamina, desmosome
What are the three microtuble forces?
Pushing, pulling, sliding
What are the roles of microtubles in interphase?
Cell motility, positioning of organelles, structural support and shape, movement of organelles and molecules
Describe the structure of microtubles
Polarised hollow tubes made from tubulin heterodimers. Heterodimers contain a and B tubulin. Form a protofilament with a + and - end, with lumen at the centre
Describe dynamic instability of MTs
Polymerisation on the + end creates growth. Catastrophe event. Depolymerisation (dissociation as curved state is putting pressure). Rescue event.
Parameters of dynamic instability:
- Rate of growth
- Rate of shrinkage
- Frequency of catastrophes
- Frequency of rescues
What is B-tubulin?
A GTP-ase. Hydrolysis forms GDP B-tubulin. Exchange/phosphorylation makes GTP b-TUBULIN
What is dynamic instability driven by?
GTP/GDP cycles. Dimer forms protofilament (straight), GTP hydrolysis changes confirmation and weakens the bond - bending. Curved protofilament with depolymersiation.
GDP-GTP exchange, formes the GTP-tubulin dimer for polymersiation again
Describe the GTP cap
+ end
B-tubulin. GTP/GDP more dynamic.
GTP added, when loss of CAP (GDP), get the shrinkage
Describe microtubule nucleation
Centrosome (spindle pole in fungi)
- main MicroTubule Organising Centre (MTOC)
- Pair of centrioles + PeriCentriolar Material (PCM + y-tubulin complex)
Nucleated from the - end
y-tubulin forms a ring complex, y-TURC forms a ring that nucleates MTs
What are the two MAPs?
Regulating dynamic turnover
tau and stathmin
Describe stathmin
Regulates MTs dynamics by sequestering tubulin dimers. Prevents subunit addition, so microtubule shrinks
Describe tau
Normally binds to MTs and stabilises them. When tau is hyperphosphorylated, it detaches from MTs so they become less stable and depolymerise.
Describe tau and tauopathies
In tauopathies (e.g. Alzheimer’s disease), Tau is hyperphosphorylated
and detaches from MTs:
1) MTs become less stable and depolymerise
2) Tau becomes insoluble and aggregates into filaments called
Neurofibrillary tangles (NFT).
Describe MTs in the context of drugs
Anti-MT drugs for human diseases
Polymerisation inhibitor = destabilise (like stathmin)
Depolymerisation inhibitor = stabilise (like tau)
Describe MTs motors
Use MTs as rails to transport organelles. Motor proteins like dynein, kinesin, myosin
Describe the two motors
Cytoplasmic dynein moves towards MT (-) end - retrograde transport
Kinesin moves towards MT (+) end (anterograde).
- 2x coordinated heads “walk”
by hydrolysing ATP
-Transport over long distances - Do not detach easily from MTs
Describe melanophores
- Certain fish can change colour in response to stimuli.
- Use special pigment containing organelles called melanophores.
- Melanophore movement along microtubules is stimulated by
hormones controlling cAMP levels, altering dynein-kinesin balanceD
Describe cilia and flagella
Contain stable microtubules moved by special dyneins. Flagella are long and single, cilia are short with many per cell
Basal body and axoneme
