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32 Cards in this Set
- Front
- Back
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Axonemes
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9 doublet, 2 central tubule structure
cilia, flagella basal body similar in structure to centrioles |
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Cellular Functions of MT
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cilia, flagella
pseudopodial movement mitotic spindle cellular transport |
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Bodliy Functions of MT
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shock absorbers for hair cells in ear
cellular differentiation- "primary cilium" sperm motility |
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Primary Cilium
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development and cell differentiation
may have either (9+2) or (9+0) composition sensory function via receptor proteins at tip--> localized on rafts on cilia cilia points in direction of movement |
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Centrosome v. Centrioles
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Centrosome= organelle containing 2 centrioles
Centrioles= 9 triplet microtubules over 1100 proteins assoc. |
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Dynamic Instability of MTs
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grow only at the distal (+) end, 13 tubulin dimers aroudn MT
tubulin dimers = α + β α = GTP binding β = GTP-binding with GTPase--> [=]GDP favors instability as long as majority [=] GTP, will stay together |
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Tubulin Dimer Characteristics
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tubulin dimers = α + β
α = GTP binding β = GTP-binding with GTPase β [=] GDP favors dynamic instability γ-tubulin = centrosomes, MT root |
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γ-tubulin
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in centrosomes
MT root protein for distal polymerization |
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Unusual Aspects of MTs
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1. Tubulin binds to many different proteins.
2. C-terminal regions of α- and β- tubulin are (-) charged--> glutamate and aspartate-->play role in signaling 3. Many post-translational modifications--> Branching, amino acid addition, etc. |
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Post-translational modification of Mts
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1. Lys40 of α-tubulin acetylated--> increase stability--> usually in axonemes
2. α-tubulin is made with C-terminal tyrosine--> may be removed or put back on (ATP-dep. and not requiring ribosome)--> more stable without 3. α + β are polyglutamated, may have branches of glutamate--> role in MAP binding 4.β-tubulin is polyglycylated--> usually in axonemes |
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Acetylation of MT
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α-tubulin Lys40 can be post-transcriptionally acetylated
acetylation adds to stability--> more common in axonemes |
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Tyrosine and MT
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α-tubuline initially made with C-terminal tyrosine
may be removed (tubulin carboxypeptidase) --> makes more stable may be added back (tubulin-tyrosine ligase) -->makes less stable ATP-dependant mechanisms |
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Branching of Tubulin
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α + β may be polyglutamated--> highly negatively charged branches-->interact with MAPS
β-tubulin may be polyglycylated--> in β-axonemes |
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Factors Adding to MT Stability
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1. Removal of α-tubulin C-terminal tyrosine
2. Polyglycylation of α + β-tubulin (axonemes) 3. Majority of subunits binding to GTP 4. α-tubulin Lys40 acetylation (axonemes) |
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Cancer and MTs
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tubulin is target for most cancer drugs--> taxanes and Vinca
anti-angiogenic--> prevents enough O2 from reaching the tumor target histone deacytylase 6--> enzyme removes acetyl group from Lys40 on α-tubulin requires only few molecules of drug to bind to end of MT--> halts growth--> cell apoptosis |
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histone deacytylase 6
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removes acetyl from Lys40 of α-tubulin
makes tubulin very stable target for anti-cancer drugs |
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Gout and MTs
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GOUT= crystalized uric acid in joints, excess uric acid
Colchicine= binds tubulin at (+) endsand freezes dynamics---> immediate releif from symptoms--> WBC can't move to site of inflammation/ secrete inflammatory factors |
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Colchine
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anti-GOUT w/ immediate relief
bind to MT and freezes dynamics WBC can't move/ secrete inflammatory cytokines |
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Joubert Syndrome
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malformation of the cerebellum--> poor coordination, retardation, breathing problems, jerky eye movements, open mouth
defect in protein TTLL6--> α-tubulin not polyglutamated-->m malformed ciliary MTs primary cilia are malformed, poor development |
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TTLL6
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defective protein in Joubert's Syndrome (cerebellar malformation)
α-tubulin is not polyglutamated--> primary cilia malformed (poor rafts to localize receptors) |
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MAPs
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Microtubule-Assoc. Proteins= bind to C-terminals of MTs--> indice stability and growth
little 2/3 structure-->promoter and projection domains phosphorylation of MAPs inhibits binding |
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Phosphorylation of MAPs
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inhibits binding to MTs
decrease MT stability |
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Alzheimer's Disease and MTs
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helical filaments inside neurons--> hyperphosphorylated TAU proteins form helical structure
amyloid phosphorylation induces helical TAU neurons unable to transpot synaptic vesticles amyloid plaques |
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Amyloid Protein
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will phosphorylate TAU protein (MAP)
hyperactivity causes Alzheimer's--> helical hyperphos. TAU and amyloid plaques |
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Myosin
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motor protein on actin
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Kinesin
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motor protein on MTs towards (+)-end
ANTROGRADE |
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Cytoplasmic Dyenin
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motor protein on MTs to (-)-end
RETROGRADE |
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Axonemal Dyenin
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MT motor protein
slides axonemal MTs against in ciliary/flagellar beating |
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Kartagener's Syndrome
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def. Axonemal Dyenin
male sterility, situs inversus, LRI situs inversus = node on neural plate has primary cilia (not able to move due to bad axonemal dyanin)--> 50% of Kartager's patients are reversed internally |
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Hereditary Spastic Paraplegia
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increasing spasticity and neuromuscular weakness
def. in kinesin (KIF5A)--> ATPase activity gone--> cannot walk on MT Kinesin mainly in neurons, inhibits antrograde transport of synaptic vesicles |
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Bardet-Beidle Syndrome
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retinopathy, polydactyl, cardiomyopathy, hypogonadism, mental retardation, obesity
def. in proteins on intraflagellar raft GPC not in primary cilia |
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Hydrocephalus and MTs
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accumulation of CSF
def. HYDIN--> contributes of axonemal motility cannot pump CSF out of brain |
