1-34 Cytoskeleton II - Intermediate Filaments and Microtubules Flashcards
intermediate filament polarity?
these are non-polar and therefor are not suited to be motility tracks
4 intermediate filament types
Keratins - epithelial cells, skin, hair
- Vimentin & Related
- Neurofilaments
- Nuclear lamins
Keratins
epithelial cells, hair nails
vimentin
desmin - junctions between keratin, strengthening
glial fibrillary acid protein: mesodermal cells
neurofilaments
neurons of both CNS and PNS
nuclear lamins
present in ALL cell types
associated with innter surface of inner nuclear membrane and with chromatin
assembly regulated by cell cycle (disassembled during mitosis via phos)
Lamin A mutations cause
Lamin A mRNA splicing defects - progeria
cancer diagnosis and treatment using intermediate filaments?
tissue type of origin can be revealed by the type of IF proteins made
demin mutations can cause
muscle weakness, heart disease
keratin mutations can cause
skin blister disease
microtubule properties
dynamic, not static arrays
structural polarity
tracks for motility
two types of motors (dynein and kinesin) move cargo (organelles or chromosomes) along microtubules
microtubules are _____ assembled from?
hollow tubes assembled from dimers of alpha/beta tubulin
assembly of microtubules
requires GTP and Mg++ and a critical subunit concentration
beta tubulin in microtubule acts as a slow GTPase, GDP must be exchanged for GTP before a subunit is re-used for assembling another microtubule
end-end binding in tail-tail orientation results in structural polarity with a fast + and slow growing - end
microtubule associated proteins and drugs can….
regulate the assembly in vitro and in vivo
microtubule dynamic instability model
- whenn all GTP hydrolyzed, plus ends disassemble quickly
- continued disassembly and assembly allow cell to change microtubule distrubution by selective stabalization of MT + ends
- this behavior allows an MT array to search cytoplasm for structures to which MT’s need to attatch to (chromosomes)
MTOCS
help do what?
microtubule organizing centers
help determine MT distribution by providing sites for the stabilization of - ends (binding)
in most vertebrate cells, the cell has one main MTOC which consists of..
paired centrioles and surrounding material which together makes a centrosome
gamma tubulin
alpha/beta tubulin related protein; found in centrosomes and functions to nucleate MT assembly
not all MT arrays are..
dynamic. the MT’s that fail to show dynamic stability have undergone “maturation”
what adds to the stability of these stable “mature” MT arrays?
post translational modifications of alpha tubulin by acetylation/detyrosination
microtubule associated proteins
serve to created specialized MT arrays in different places within cells and tissues and change the surface of the MT’s for interaction with other cellular proteins
can also stabalize MT’s to decrese their probability of disassembling
dyneins
Inward Motor
one, two, or three headed ATPases that produce (-) end directed motility
cytoplasmic dyneins are 2 headed
cilia and flagella have 1 and 3 heads
Kinesins
Outward motor
2 headed atpase that produce + end motility (outward)
kinesin and dynein transport vesicles in nerve axons
outward transport (like neurotransmitters)
inward transport (like recycled membranes) use dyneins
In Cilia, MT do what?
push out membrane, like actin meshwork
cilia and flagella have…
conserved structure in a 9+2
cilia and flagella are cylinders of..
they may be?
9 doublet microtubules that project from the cell surfce and are surrounded by PM.
motile, sensory, or both.
axoneme
the doublet MT’s and associated proteins
basal body?
protein structure found at the base of cilia/flagella that is formed from a centriole and serves as a nucleation site for the growth of axoneme MT’s
motile flagella are found on..
sperm
cilia can be found on…
airways, fallopian tubes, brain ventricles
embryonic cilia generates..
body plane symmetry seen in adult organs such as heart, kidneys, liver
wave types of cilia vs flagella
cilia - asymmetrical wave
flagella - symmetrical
what produces movement of cilia and flagella?
MT sliding
regulated sliding results in localized bend formation
waves of dynein activity become waves of bend propogation
Bend propagation-bends in one direction require activity of dyneins between doublet MTs along one side of the flagellum. In order for the flagellum to bend the other direction, the first set of dyneins must be inactive while a second set along the other side of the flagellum is active
general structure of intermediate filaments
built from long, helical subunits
- initially forms dimer between subunits
- molecule has polarity in dimer form, but loses polarity in the tetramer form (not good motility track)
microtubule assembly - dynamic instability model in vivo
Tubulin binds GTP; only the GTP-bound form assembles.
Beta tubulin in assembled dimers can hydrolyze its GTP to GDP.
If assembly is faster than hydrolysis, the microtubule grows.
If assembly is slower than hydrolysis, the microtubule becomes unstable.
Unstable microtubules shrink rapidly, but may be ‘rescued’ by binding new GTP tubulin dimers at the end, and resume growth.
gout treatment?
colchicine that blocks microtubule formations
cancer treatments?
drugs that disrupt tubes in mitotic functions. must be able to assemble and disassemble the MT’s for mitosis
vinblastine
cancer treatment, blocks MT assembly in mitosis
TAXOL
stabalizes assembly of MT, disrupts mitosis. no longer “dynamic”
centrosome
where the (-) ends organize, plus ends radiate out.
1 per cell
most interphase cells have a single
MTOC
tubule maturation
some microtubules are stablized by post trasnlational modifications (Acylation of lysine residue) and stop being dynamic.
MAPS
microtubule may be stabalized by capping proteins or MAPS
the microtubules in cilia are
stable. not growing and shrinking
positioning of the ER and golgi relies on
microtubules and motor proteins
- kinesin stretches the ER from the nucleus out towards the microtubule+ ends
- dyneine keeps the golgi near the nucleus (-) end
PCD, primary ciliary dyskinesia
mutation affecting ciliary motility, causes infertility (males), respiratory infections, development of assemetrical defects
situs solitus
situs inversus
heterotaxy
ss - heart backwards
si - everything backwards
h - everything in the center (problematic)
Polycystic Kidney Disease
mutation affecting ciliary membrane receptors
-caused by lack of receptors int he membrane on non-motile cilia in kidney tubules
non motile cilia are needed for
many sensory systems and during limb development. Loss of these cilia results in wide range of symptoms
Bardet-Biedl Syndrome
sensory cilia defect - obesity, diabetes, hearing loss, retardation, polycystic kidneys, retinal degenertion
bacterial flagella nd eurkaryotic flagella are..
unrelated
motile cilia are
cynlinders of microtubules that bend
