Cytoskeleton Flashcards
What is the cytoskeleton?
Network of protein filaments throughout cytoplasm
What are the functions of the cytoskeleton?
Mitosis + Cytokinesis Traffic Support Cell shape Muscle contraction
What are the 3 types of cytoskeleton filament?
Intermediate filaments
Microtubules
Actin filaments
What to intermediate filaments do?
Where are they abundant?
Provide tensile strength
Cells subject to mechanical stress e.g. muscle cells
What are the 3 main classes of intermediate filaments?
Keratin filaments
- epithelial cells
Vimentin filaments
- connective tissue cells, muscle cells + supporting cells
Neurofilaments
- nerve cells
What are nuclear lamins?
Intermediate filaments found just under nucleus membrane
What are intermediate filaments made of?
Monomers with a central rod domain + globular region at either end
Describe the construction of an intermediate filament
- Monomers dimerise
- 2 dimers line up to form a staggered tetramer
(N terminus near C terminus of other dimer) - Tetramers pack together end to end
- 8 tetramers twisted into a rope
How do keratins connect neighbouring cells?
Indirectly connected to filaments of other cells through desmosomes (cell-cell junctions)
How do keratins indirectly connect cells via desmosomes?
Cadherins span the 2 membranes
-> bind the 2 cells together
Give an example of an intermediate filament disorder
Epidermolysis bullosa simplex
= keratin cannot form normal filaments in the epidermis
-> skin v susceptible to injury
What is the difference between lamins + laminins?
Lamins = cytoskeleton proteins
Laminins = ECM proteins
Why are intermediate filaments v stable, strong + durable?
Extensive protein-protein contacts
Describe actin filaments
In all eukaryotic cells
Made up of globular monomers that associate head to tail
Unstable w/out associated proteins
When do F-actin filaments form?
Spontaneously from G-actin above the critical conc
In the presence of ATP, Mg + K
Describe the polymerisation of actin
- Actin monotoners in cytosol carry ATP
- ATP hydrolysed -> ADP after monomers assemble into filament
- ADP replaced with ATP when actin disassembles from filament
Which proteins bind to actin to modify its properties?
Monomer binding proteins Nucleating " Cross-linking " Capping " Bundling " Motor "
What are 2 drugs that act on the actin cytoskeleton?
Cytochalasin D
- binds to +ve end of F-actin
- > prevents further addition of G-actin
Phalloidin binds F-actin + prevents actin filaments from depolymerising
What are the 4 functions of actin?
> Mechanical strength + cell shape
Cell crawling
Muscle contraction
Organelle movement
What is cortical actin?
Actin filaments concentrated in a layer in the cortex
- linked into a meshwork by actin binding proteins
What is cell crawling?
Filopodia or lammelipodia extend a region of plasma membrane
(driven by actin cytoskeleton rearrangement)
Integrins adhere to ECM
Cells use internal contractions to pull itself forward
Which family of proteins do actin dependent motor proteins belong to?
Myosin family
How does mysosin move along actin filaments?
Myosin binds + hydrolyses ATP
-> provides energy
= moves from - to + end
Describe microtubules
Long, hollow cylinders made of tubulin
Most rigid + straight type of filament
How are microtubules assembled?
From tubulin made up of a dimer of alpha + beta tubulin
What maintains microtubules?
Balance between assembly + disassembly:
Cell contains mix of microtubules + free tubulin
Microtubules = unstable = undergo rapid remodelling
Where do microtubules grow out from?
Centrosomes
microtubule organising centre
What controls the growth of microtubules?
GTP hydrolysis
What controls the growth of microtubules?
GTP hydrolysis
If new subunits (which have GTP bound to beta tubuilin) are added quicker than beta tubules hydrolyse GTP
-> GTP cap forms
= growth
GTP hydrolysis faster
-> GTP cap lost
= shrinkage
How are microtubules stabilised?
By probing the environment in search of interacting proteins
What are the 3 functions of microtubules?
> Cellular organisation, movement of organelles + cell polarity
> Cell division
> Cilia + flagella
What are the motor proteins associated with microtubules?
Kinesins
Dynesins
What do kinesins and dynesins have in common?
Both have 2 ATP binding heads + a tail
Both have ATPase activity
Kinesins move towards +ve end
Dynesins move towards -ve end
What enables motor proteins to move along microtubules?
What does the tail attach to?
ATP hydrolysis provides energy for conformation changes in the head
-> cycle of binding, release + re-binding
Cargo
How do microtubules organise cells?
ER pulled outwards along microtubules by kinesins
Golgi apparatus pulled in other direction by dyneins
What are 2 drugs that interfere with microtubule assembly?
What affect do both of these drugs have?
Colchicine - binds free tubulin + prevents polymerisation into microtubules
Taxol - binds to microtubules + prevents them losing subunits
Both are anti-mitotic
What do cilia and flagella contain?
Stable microtubules that’s moved by dynein
How do cilia move?
Repetitive cycle of power stroke then recovery stroke
Bending is driven by Dynein
Why do cilia + flagella bend?
Nexin links are stable
-> walking of dynein along microtubule causes bending rather than sliding