Lecture 4 - The Cytoskeleton: Microtubules Flashcards
Basic details of the 3 main types of cytoskeleton:
- What a protofilament is
- How they are nucleated
- Cellular roles for each type of cytoskeletal polymer
- Properties of MFs and MTs
- The existence of ABPs and MAPs
- Molecular motors
- How they work
- What they do
- Some examples
Functions of the cytoskeleton
• Bones and muscles of the cell
- cell shape/polarity
- cell motility
- cell plasticity
- segregation of chromosomes
• Railways of the cell
- endocytosis
- secretion
- segregation of organelles
- communication between organelles
- Many diseases associated with cytoskeletal abnormalities
- Route of entry for many bacterial and viral pathogens
Networks of intracellular filaments
Microtubules
- centrosome (MTOC)
Intermediate filaments - nuclear lamina, desmosome
Actin filaments (microfilaments) lamellipodium, stress fibre
Microtubules ILOs
o Function
o Structure
o Dynamic instability
o GTP cap
o Nucleation
o Regulators
o Links to disease
- Describe in some details how microtubules function
- Describe in some details how microtubules are nucleated
- Describe in some details how microtubules are regulated, notably by MAPs.
- Start to understand the implications of all of the above, for health and disease
- Interpret scientific data
Role of microtubules in interphase
- Structural support and shape
- Cell motility
- Positioning of organelles
- Movement of organelles and molecules
Role of microtubules in mitosis
- Chromosomes alignment and segregation
- Partitioning of organelles between daughter cells
- Definition of the site of cytokinesis
Microtubule structure and properties
Microtubules (MTs) are polarised hollow tubes made of tubulin heterodimers
alpha is always at the minus end
beta is always at the plus end
13 protofilaments make a MT
diameter of MT is approx 25nm
Dynamic instability of MTs
Parameters of dynamic instability:
‐ Rate of growth
‐ Rate of shrinkage
‐ Frequency of catastrophes
‐ Frequency of rescues
Data Handling Practice
Answer:
Microtubules are polarised
o The ‐ end is less dynamic, ie the 4 parameters are decreased.
o The 2 ends are not the same = polarised
o If grows faster at the + end and shrinks less at the – end, then, the
MT will necessary grow from its + end. Same for shrinkage!
Dynamic instability occurs at both ends, just faster at the plus end!
B‐tubulin is a GTPase
‘ase’ means it’s an enzyme
so b-tubulin is a GTP modifiying enzyme (hydrolyses GTP to GDP)
a-tubulin will bind GTP but does nothing to it
Dynamic instability is driven by GTP/GDP cycles
The GTP cap
The + end
= B-tubulin
= GTP/ GDP
= more dynamic
GTP cap protects the end of the microtubule, GDP is unstable -
GTP is added faster than GDP lost which is why you get growth and catastrophe - this is why you get the GTP CAP
How are microtubules formed (nucleated)?
Microtubule nucleation
Centrosome (spindle pole body in fungi):
‐ main MicroTubule Organising Centre (MTOC)
‐ Pair of centrioles + PeriCentriolar Material (PCM + ‐tubulin complex)
MTs are nucleated from the ‐ end
gamma tubulin makes the TUSC (G-tubulin Small Complex) and the TURC (G-tubulin Ring Complex)
centrosome is at the centre of the cell, all microbules come from it