Scaffolds of the cell Flashcards
What are the 3 major components of the cytoskeleton?
Actin microfilaments
Tubulin microtubules
Intermediate filaments.
All filaments are made from smaller subunits.
The cytoskeleton is dynamic.
What are the roles of microtubules in cells?
Maintenance of cell shape.
Swimming and surface movement of fluids - cilia.
Formation of mitotic spindle.
Tracks for movement of vesicle, organelles, proteins.
What are microtubules made from?
Made from the protein tubulin.
Tubulin is a dimer of 100kDa made from a and B subunits.
What is the structure of tubulin?
3 a- genes and 8 B-genes.
Each tubulin can bind 2 GTP molecules (1 in each subunit).
Only the GTP on the B-tubulin is hydrolysed, giving the dimer polarity.
What is the structure of microtubules?
The dimers can assemble in head-to-tail fashion due to its polarity, and forms protofilaments.
13 protofilaments form in a ring structure to form a hollow microtubule.
Where else does polarity come from in microtubules?
There is a slight shift in alignment of protofilaments, because they are not lined up exactly.
What is the polymerisation of microtubules?
Tublin monomers form dimers.
Dimers polymerise into oligomers.
Oligomers grow into linear protofilaments and microtubules.
Microtubules elongate by reversibly adding dimers.
Why is there a lag at the start of polymerisation?
Initial forming of a- and b- dimers to form oligomers is rate limiting.
Once the core oligomers form, it forms a nucleus which the rest of the microtubule rapidly forms from.
Why is the MTOC important?
Microtubule organising centre contains pre-formed microtubule rings of oligomers.
So the cell can very quickly grow microtubules when needed.
What is dynamic instability?
Microtubules may grow steadily, and then shrink rapidly by loss of tubulin dimers from the positive end - the catastrophe.
This happens when GTP is hydrolysed to GDP.
Why is GTP hydrolysis important?
It means the cell can rapidly turnover old filaments by hydrolysing the GTP to GDP, which causes the microtubule to be unstable.
What are the classes of microtubules binding drugs?
Tubulin dimer binding
Tubulin polymer binding
What are tubulin dimer binding drugs?
Drugs bind to dimer and prevent polymerisation.
e.g. Colchine, Vinblastine, Nocodazole
What are tubulin polymer binding drugs?
e.g. Taxol, can bind to polymer, and stabilises the microtubule and stops it falling apart, and being turned over.
What is the use of Taxol in disease?
Taxol targets some cancers such as ovarian and breast, by targeting the mitotic spindles and preventing them from forming.
