The cytoskeleton Flashcards
What is the cytoskeleton
A network of protein filaments extending throughout the cell determine the cell shape and polarity
What are the three types of cytoskeletons- from smallest to largest ?
Actin
Intermediate Filaments
Microtubule
Describe the structure of actin
The filaments are called F-actin and they are composed of G-actin ( monomers- individuals actin proteins)
It is a polarised double helix- hence why it will be striped in pictures
Diameter=7nm
13 actin subunits for a complete turn
Actin filaments are described to be dynamic- what is meant by this?
It has the ability to change shape
The G actin can be added and removed from both plus and minus ends of the polymer.
The monomer is more readily added to the plus end of the filament
G actin needs to be bound ATP- hydrolysed to ADP
What are the major functions of actin?
Mechanical support
Cell Shape changes and maintenance- RBC and adherent junction
Cell Motility
Summarise and list the actin binding proteins
Motor Proteins eg myosin in muscle
Membrane attachment proteins eg Spectrin
Cross linking proteins eg transgelin
Capping proteins (prevents filament growth)
Side binding proteins (allows the interaction with other proteins)
Severing proteins (severin,gelesdom)
Actin-Bundling protein- Alpha actinin in muscle
What are actin sequestering proteins
Bind to G actin preventing it from polymerising
eg. profilin, thymosin
Describe the structure of intermediate filaments
Polymer of individual intermediate filament proteins
10nm in diameter
Networks typically most dense around the nucleus- extends to the periphery
Intermediate filament proteins form cross
What are the major functions of the intermediate filaments
Anchor cell at the some junctions
Support nuclear structure
Describe the formation of the intermediate polymer
1) intermediate filament protein- monomer
2) Helical dimer
3) 2 dimers combine to form a tetramer- the fundamental unit of IF
4) Tetramers link in a staggered formation end to end to form the filament
5) Subunit exchange os slow but occurs along the length of the whole filament
NB proteins bind to the IF to modulate the function
Plectinin molecules link IFs to actin filaments
Describe the structure of microtubules
Long relatively stiff hollow tubes (approx 25nm diameter)
Visible by EM/light microscope
Can be rapidly assembled and deassembled
The polymer is built from monomers of tubulin- one monomer which has alpha tubulin and beta tubulin.
Therefore the molecule is asymmetric and so polymer has polarity- one end start with alpha, the other beta
How are microtubules assemble (and deassembled)
Monomers bind to GTP
And are added to plus end
The monomers gradually lose the GTP as it is dephosphorylated- LOSES AFFINITY
Microtubule polymerises in centrosome ( minus stays close to the centrosome and plus toward the periphery)
What are the uses for cytoskeleton
Cell Shape and orientation Anchoring the organelle Anchoring the cells Cell Motility Movement
Describe the “cell shape and orientation” aspect
Actin filament bundles provide support
Actin filament sheets also provide support-
1. dense sheets of actin- found in cortex of cell
2. Maintains the shape of cells eg erythrocytes
eg Stereocillia in the inner ear-
cells are depolarised/hyperpolarised by deflections caused by sound. Here, actin filaments keep stereocillia rigid despite the vibrations of sound
Intermediate filaments stabilise the shape of axons (soma - synapse)
Microtubules stabilise the shape of platelets (formed instantly when stimulus applied)
Describe the “anchoring cells” aspect
The cytoskeleton is essential to anchor the cells to each other and extracellular matrix at cell junctions
eg at adherens junctions- forming adhesion belt due to the cadherin dimer being held by actin
Describe the “anchoring the organelles” aspect
Microtubules organise the ER of a cell
IF form a meshwork around the nucleus of a cell nucleus (LAMINA) to hold in position the transcription machinery- keeping it ordered (anchored)
Actin is also required to hold the synaptic vesicles close to the presynaptic membrane
Describe the “ Cell Motility “ aspect (actin based movement)
Actin Based Movement-
1) Cell pushes pushes out protrusions at the front- actin filament polymerisation provides the force for membrane protrusion
2) Protrusions adhere to the surface to the surface on which the cell is moving through focal contact junctions
F actin connect to focal adhesions to provide a contractile force for the cell
3) The rest of the cell pulls against the anchorage point to drag itself forward
4) Actin depolarises at the rear
Explain the example of Lamelipodia
Lamellipodia- samples the environment, extends and withdraw
generated by rapid growth of actin filaments at the cell membrane. The plus end of the actin filaments are orientated towards the periphery of the cell
When the lameilpodia touches down on the surface, they attach onto the ECM through the formation of the focal adhesion (integrins).
The actin filaments are crucial in the sense that they connect the focal adhesion to the rest of the cytoskeleton
The actin filaments are then pulled upon by myosin to drag the cell forward.
The myosin head interacts with actin having been bound to ATP
energy released from the ATP hydrolysis forces myosin head to move. ADP released from the head and the head detaches from the actin filament.
Describe cell motility aspect ( microtubule)
eg. Cilia lining respiratory epithelium-
have a structure of: 9 double microtubules periphery and 2 in the middle
The movement is initiated by dynein- a minus end directed motor proteins
microtubules slide along each other which causes the cilia to bend
They are anchored to the CSM which allows for the swaying movement
Describe the “movement of intracellular contents and organelles
Microtubules- allows for movement of organelles eg. synaptic vesicles from axons- synaptic cleft.
2 Motor protein- kinesin and dynein
Kinesin moves towards the positive end (cell periphery)
dynein moves towards negative end ( nucleus)
Contrast the function of kinesin and myosin
Kinesin Stays attached to the microtubule throughout ATP hydrolysis cycle- processive motor protein- significant movements
Myosin II detaches completely from actin filaments at the end of the cycle- not processive
Describe the action of chemotherapeutic agents
Colchine, vinbalstine (destabilise microtubules)
taxol (stabilises microtubules)
Both inhibit function of mitotic spindle- therefore cell division
Describe how cytoskeleton abnormalities lead to disease
With actin- mutations in dystrophin can cause Duchenne Muscular Dystrophy
With IF- epidermis bullosa symplex- mutations in keratin genes= failure to form proper keratin filaments- skin is highly sensitive to mechanical injury- blistering in adults and sloughing of epidermis in newborns.
- ALS- hereditary forms of mutations in neurofilamin genes
With Microtubules- Alzheimers disease- amyloid plaques- AD brains display neurofibrillary tangles
Describe the hijaking of actin cytoskeleton by listeria bacteria
Listeria engulfed by host cell
The bacterium escapes from the phagocytic vesicle
F-actin is polymerised at the back of the bacterium providing motility
The actin comet drives the bacterium into the neighbouring cell
