cytoskeleton Flashcards
what are the 3 filament types (smallest to largest)
- actin (microfilaments) - actin-binding proteins
- intermediate filaments
- microtubules: microtubule-associated proteins (MAPs)
describe actin structure
- F-actin
- polymers of actin proteins called G-proteins
- polarised double helix
how many acts subunits for each complete turn? diameter?
13
7nm diameter
explain growth of actin filament
- ATP bound to actin monomer (G-actin)
- monomers added/removed from both ends of polymer
- add more rapidly to +end
- once incorporated, ATP –> ADP
3 main functions of actin
- mechanical support
- cell shape changes and maintenance
- cell motility
9 functions/roles of actin proteins
- G-actin monoers
- actin-sequestering proteins (eg. profilin, thymosin) prevent G-actin polymerising
- actin-bundling proteins (a-actinin in muscle))
- motor proteins (muscle myosin)
- side-binding proteins (interact w other proteins)
- capping proteins (prevent growth)
- cross linking proteins (eg. transgelin)
- severing (gelsolin, severin)
- membrane attachment proteins (spectrin)
diameter intermediate filaments
10nm
visible by e.m.
functions of intermediate filaments
- dense around nucleus
- anchor cells at some cell junctions
- support nuclear structure
examples of intermediate filaments
Named vary by cell types:
eg. keratin, vimentin, glial fibriallary acidic protein, neurofilamin
how is an intermediate filament polymer formed
- monomer
- helical dimer (2 monomers)
- 2 dimers combine = tetramer (fundamental unit)
- tetramers link - staggered formation
- Subunit exchange is slow but occurs throughout the length of the filament.
example of modulation of IF
plectin molecules link IFs to actin filaments and microtubules
diameter microtubules
25nm
visible by e.m. or light microscopy
describe structure of microtubules
- polymer built from TUBULIN monomer which consist of one molecule of a-tubulin and beta-tubulin
- asymmetric monomer: polymer has polarity (one end stops with a, one with b)
describe arrangement of columns of tubulin
13 columns of tulip polymer arranged in hollow cylinder
assembly and disassembly of microtubule
- (negative) end: GPD bound monomers dissociate rapidly
- GTP bound monomers assemble onto + end
GTP–>GDP, cycle starts again
where are microtubules polymerised
centrosomes
minus end remains close to centrosome, plus end points out towards cell periphery
how does cytoskeleton help cell shape and orientation
- actin: support. maintain shape of cell e.g. erythrocytes
- IF: stabilise axon shape
microtubules: stabilise shape of platelets and axons
how do stereocilia detect vibration in cochlea
The cells are depolarised or hyperpolarised by deflections caused by sound.
Actin filaments keep the stereocilia rigid.
how does cytoskeleton help anchoring organelles
- actin: hold synaptic vessels close to presynaptic membrane
- IF: hold cell nucleus
- microtubules: organise ER of a cell
- cytoskeleton holds cell next to each other and to extracellular matrix at cell junctions
describe 4 steps of actin-based cell movement
- leading edge - cell push forward. actin polymerises
- focal contact junctions allow adherence of projections. F-actin connects focal adhesions
- backside of cell pulls against anchorag epounts
- actin depolymerises at rear
what are lamellipodia and how do they function
- sample environment - extend and withdraw
- plus end of actin orientated to cell periphery
- When lamellipodia or filopodia touch down: attach to the extracellular matrix through the formation of focal adhesions (focal contacts)
- Actin connect the focal adhesion to the rest of the cytoskeleton
how does myosin help actin
myosin II: motor protein
- head region interacts w actin and binds ATP. Energy release from hydrolysis = myosin tail moves
- ADP released from head and replaced by ATP = detach from actin
- head binds further down filament
describe microtubule based movement
- cilia
- 9+2 structure
- DYNEIN (a MAP): initiate movement. minus end-directed motor protein
- microtubules slide along each other = bend cilium
how does cytoskeleton help movement of intracellular contents
microtubules
e. g. move synaptic vessels along axons to synapse
- motor proteins kinesin (moves to + end) and dynein (moves to - end) move vesicles
what’s the difference in the action of kinesis and myosin II
- kinesin stays attached to microtubule during ATP hydrolysis = processive motor protein. moves large distances
- myosin II: detaches from actin at end of the cycle, travel short distances
e..g. when cytoskeleton is used tome cell contents
separation of chromosomes during cell division - microtubules
3 anti-cancer therapeutics and their mechanism
colchicine, vinblastine, taxol
- inhibit function of mitotic spindle and thus cell division
- C&V: destabilise microtubules, T stabilises
actin abnormalities leading to disease
- mutation in dystrophin = Duchenne and Becker Muscular Dystrophy
- mutation in myosin VII = Usher’s syndrome - heriditary deafness and blindness
intermediate filament abnormalities leading to disease
- Epidermolysis bullosa symplex
- Amyotrophic Lateral Sclerosis (ALS, Lou Gehrig’s Disease)
microtubule abnormalities leading to disease
- Alzheimer’s Disease
- Hereditary Spastic Paraplegia
how does Listeria bacteria affect actin cytoskeleton
- engulfed by host cell
- escapes
- F-actin polymerises at back of bacterium = motility
- drives bacterium into neighbouring cell
what is Epidermolysis bullosa symplex.
IF
- Mutations in keratin genes= failure to form proper keratin filaments in epidermis
- skin sensitive to mechanical injury
- Blistering in adults, sloughing of epidermis in newborns
- Plectin mutations also cause EBS with muscular dystropy
Amyotrophic Lateral Sclerosis
IF
(ALS, Lou Gehrig’s Disease).
-Some hereditary forms are caused by mutations in neurofilamin genes
-causes of motor neuron degeneration are unclear.
Alzheimer’s Disease.
microtubules
- Alongside amyloid plaques, AD brains display neurofibrillary tangles comprising the MAP, Tau.
- Tau is hyperphosphorylated in tangles and cannot bind MTs.
Hereditary Spastic Paraplegia
microtubules
The most common form is caused by mutations in spastin, a microtubule severing protein.
