Micro - Cytoskeleton 8/14 Flashcards
Microtubules
tubulin heterodimers - alpha/beta tubulin
Hollow cylinders
gamma tubulin - helps nucleate (found in centrosome/MTOC)
MT properties
highly dynamic
polarized - + end is more dynamic
- end is in the MTOC
MT functions
Mitotic spindle railways Cell shape Cilia, flagella centiroles, basal bodies
MT instability and growth
Dynamic instability
Alpha/Beta GTP - assemble
GTP hydrolysis happens after time
MT catastrophe
cycle of growth ends and disassembly begins
GDP dimers dissociates
MT Rescue
When shrinkage stops and growth starts
Taxol
stabilizes MTs
Colchicines
prevent tubulin polymerization
vinblastine
depolymerize MTs
Kinesin
+ end on MT
Dynein
- end on MT
MT motor protein structure
Head binds to MT - determines direction
Tail/base - binds cargo
Use ATP to move
MAPs for MTs
Tau
organize MTs into bundles or irregular meshworks
regulative stability
MT nucleation and polymerization
Nucleation only happens at centrosome and takes a long time
Polymerization is rapid
y-tubulin required for nucleation but is not incorporated
MT in cell division
Centrioles replicate Types Astral - radiate to cortex Kinetochore - bind to chromosome Polar - mix with opposing MTs
Cilia/flagella
Both generate movement
Grow from a basal body (9 triplets MT)
Axoneme - core with 9+2 MTs
Ciliary dynein generates sliding force and beating
Immotile Cilia Syndrome
results in obstructive lung disease, sterile males
Kartagener’s Syndrome
combo of immotile cilia + situs inversus
Cilia normally establish the axis
POlycystic kidney disease PKD
kidney failure due to numerous cysts from epithelium of kidney tubules
Loss of functional cilia
Bardet-Beidl syndrome
Blindness due to loss of photoreceptors of retina
Cilia/basal bodies
Spastic paraplegia
MT severing protein leads to spinal cord degenerative diseases
Cancer therapies
Taxol - overstabilize MTs
Actin composition
Nonhollow polymers of G actin
Helical
Actin properties
Very highly dynamic
Can have different shapes/forms
Substrate for myosin motor proteins
Do not form organizing centers
Actin nucleation
can happen anywhere
Arp2/3 complex - branched filaments
Formins - produce bundles of parallel unbranched filaments
Actin polarization
Barbed + end - highly dynamic
Pointed - end - more stable
Myosins move towards the barbed end
Actin functions
attach cytoskeleton to plasma membrane
contractile ring for cleavage furrow
cell motility
short-range organelle transport
Actin filaments
Helical
Alpha, beta, gamma
Alpha - muscle only
Beta, gamma - all cells
Actin polymerization
ATP dependent (GTP for MTs) After addition the ATP is gradually hydrolyzed G actin monomers --> F actin polymer Nucleation is slow, elongation fast Arp2/3, formins
Acting Binding Proteins
sequester actin molecules, capping, cross linking actin, severing, annealing
Actin stress fiber
bundle of many actin filaments in parallel (formin)
Myosin - contraction
Alpha-actinin - stabilizes bundles
Leading edge
Arp2/3 makes filaments that start to push out and extend the filopodia
Actin Myosins
Use energy from ATP hydrolysis to move
Move toward barbed + end
Undergo conformational change that results in force generation
Microvilli
Actin based structure - increase surface area or detect sound
Bundle of actin as core
Myosin link the actin to the plasma membrane
Fimbrin/villin
proteins that cross link the actin filaments in the microvilli
Myosin I attach the central bundle to membrane for movement
Terminal web
Bottom of microvilli
Actin and intermediate filaments
Stereocilia
long microvilli - actin based
Hereditary spherocytdosis
deforms red cells to fragile spherocytes due to mutations in spectrin
RBC cytoskeleton
shape is determined by cytoskeleton
Network of spectrin molecules joined by protein complexis
Intermediate filaments
non-polarized
non-dynamic
diverse
Most structural role
IF Functions
space filling
tensile strength
can have specialized functions
desomosomes and hemidesmosomes
IF structure
two monomers form a coiled-coil dimer
2 dimers in antiparallel = tetramers
tetramers –> staggered pattern
NO ATP/GTP needed
Type I: Acid Keratins
IF
epithelial cells, nails, hair, diverse
Type II: Neutral/basic keratins
IF
epithelial cells, nails, hair, diverse
Type III IF
Vimentin - fibroblasts
Desmin - muscle cells
GFAP - glial cells
Type IV IF
Neurons
Type V Nuclear Lamins A/B/C
nuclear lamina of all nucleated cells
Progeria
IF disease
Fast aging disease of lamina proteins (lamin A)
