Cell mobility and cytoskeleton Flashcards
What does the cytoskeleton do?
Movement of substances around cell, controls cell shape
What are the constituents of the cytoskeleton?
Actin microfilaments
Intermediate filaments
Microtubules
Describe actin
F-actin is a polymer of g-actin.
Helical polymer 13 subunits/turn
polarised (+/- end)
How does actin grow
Actin monomers can be added or removed from either end of the molecule, but is added more quickly at the plus end.
Addition of a monomer requires ATP.
What are the functions of actin?
Mechanical support
Changes cell shape
Cell motility
What are the types of actin binding filaments and give examples
Capping Severing (severin, gelsolin) Cross-linking - transgelin Side-binding Motor Bundling (a-actinin) Sequestering (profilin, thymosin) Membrane attachment (spectrin)
Intermediate filaments
Polymer of individual intermediate filament proteins - used to anchor cells at some junctions to other cells or to a basal membrane
Describe the formation of an intermediate filament polymer
2 helical dimers form a tetramer; which link in a staggered formation end to end
What does plectin do
Links IFs to actin and microtubules
Describe microtubules
Rigid, roughly 25nm in diameter.
Made of tubulin alpha and beta monomers in a spiral with 13 columns
Plus end at B side, minus at a
How do microtubules grow
GTP hydrolysed to GDP in addition of tubulin
Where are microtubules made
Centrosome, minus end of microtubule remains close to the centrosome while the plus end extends into periphery
What is the function of the cytoskeleton?
Cell shape + orientation Anchoring organelles Anchoring cells Cell motility Movement of intracellular contents and organelles
How does the cytoskeleton aid cell shape and orientation?
Actin filament bundles provide support such as in microvilli; but microvilli sheets can maintain the shape of a cell (like in erythrocytes)
Stereocilia in the ear are depolarised/hyperpolarised by deflections caused by sound - actin keeps them rigid.
Intermediate filaments help maintain the shape of axons.
Microtubules stabilise the shape of platelets and axons
How does the cytoskeleton help anchor organelles?
Actin hold synaptic vesicles close to the presynaptic membrane; microtubules organise the ER; intermediate filaments form a meshwork around the nucleus of a cell to hold it in position.
How does the cytoskeleton help anchor cells
Cytoskeleton anchors the cells to each other or to a basal membrane via junctions
How does the cytoskeleton aid cell motility
Protrusions pushed out by the cell - actin filament polymerisation provides the force
Protrusions adhere to the surface of the ECM via focal contact junctions
F-actin connects to focal adhesions to provide contractile force
Then the rest of the cell pulls against anchorage proteins to drag itself along
What are lamellipodea
Exploratory and motile protrusions in the cell surface membrane, produced by the polymerisation of the + end of actin filaments.
They sample the environment, extend and withdraw.
How do lamellipodia attach to the surface of the ECM?
Via formation of focal adhesions, which are integrins
How do lamellipodia contribute to cell mobility
Protrusions attach to the ECM via focal adhesions (integrins) then myosin II pulls against it.
How does myosin II help with cell motility
It pulls against the actin filaments in lamellipodia.
The head region of the actin filaments interact with actin and bind ATP
ATP is hydrolyses so the tail of the myosin moves.
ADP released from myosin head, replaced by ATP.
Myosin head detaches from actin and binds again further along the filament.
Where and how do microtubules help with movement?
In cilia and flagellae, in respiratory epithelium.
Movt initiated by dyenein (microtubule associated protein) a minus end directed motor protein.
Microtubules bend over as dynein proteins move relative to each other causing microtubules to bend.
How does the cytoskeleton help with movement of organelles?
Microtubules can act as a railway to help guide the movt of organelles.
Kinesin and Myosin II are the motor proteins involved.
Kinesin is a processive motor protein which ‘walks’ along the microtubule towards the + end of the microtubule.
Dynein moves towards - end
Myosin II jumps short distances, detaches completely from microtubule.
What is dynein?
A minus end directed motor microtubules associated protein.
What are some chemotherapeutic agents that interact with the cytoskeleton in the treatment of cancers?
Colchine + vinblastin destabilise the microtubules
Taxol stabilises microtubules
Both inhibit function of mitotic spindle so cell cannot divide.
What is Duchenne muscular dystrophy?
Mutation in dystrophin, a protein that links actin component of sarcomere to sarcolemma, stabilising it like a shock absorber.
Over time contractile tissue is replaced with fibrous tissue.
What is Usher’s syndrome
Hereditary blindness, deafness due to myosin VII mutation
What is Epidermolysis bullosa simplex
Mutation in keratin gene means proper keratin filaments do not form in the skin, blistering in adults and sloughing of skin in newborns. Also caused by plectin mutations but will also have muscular dystrophy
What is EB/EBS
Epidermolysis bullosa (simplex)
What is ALS and what causes it?
Amyotrophic lateral scelerosis
How can the cytoskeleton contribute to Alzheimer’s disease
Microtubule associated protein Tau hyperphosphorylated in tangles and so cannot bind to MT’s
What is hereditary spastic paraplegia
Mutation in spastin, a microtubule severing protein.
What is the diameter od microtubule
25nm
How many coloumns make up a microfilament
13
Describe the process of building a microfilament
GTP bound monomer bind to + end and are hydrolysed to being GDP bound
vise versa for deconstruction
Describe kinesin
moves vesicles towards periphery
Describe dyenin
moves vesicles towards nucleus
