Term
| Name an important cytoskeleton function. |
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Definition
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Term
| Name the associated motor proteins of cytoskeleton |
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Definition
Microtubules:
Dynein
Kinesin |
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Term
| Name the structure, protein subunits, and main functions of Microtubules |
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Definition
Hollow tubes
Tubulin
Alpha and Beta (these dimerise)
Maintain cell shape
Motility
Chromosome movements
Organelle movements |
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Term
What are the functions of microtubles?
4
Example..."railroad"...for what? |
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Definition
Structural component:
Resist compression “support beams” = Most rigid of filaments
Intracellular transport (organelles, vesicles)
Forms spindle apparatus in mitotic cells
Act as motile elements in cilia & flagella
Example:
Organise ER & Golgi apparatus: “railroad” connecting...
trans golgi network to cell surface
early endosome to late endosome & lysosome compartments |
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Term
| How do microtubules polymerize? |
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Definition
α & β-tubulin dimers polymerise end to end:
α subunit (- end) contacts β subunit (+ end) of next dimer → polar tubes
Dimer is alpha and beta together |
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Term
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Definition
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Term
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Definition
| Its on single strand of a whole bunch of tubulin heterodimers. Linear arrangement x13 |
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Term
Describe the differences between
GTP-bound β-tubulin and
GDP-bound β-tubulin |
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Definition
β-tubulin : capped with GTP
β-tubulin hydrolyses GTP to GDP shortly after assembly
GTP-bound β-tubulin: α/β dimer has high affinity for other subunits
GDP-bound β-tubulin: α/β dimer has lower affinity |
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Term
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Definition
Remember:
β-tubulin GTP gradually hydrolysed to GDP + Pi
There is a GTP cap
BUT
If GDP-tubulin reaches growing end → depolymerisation = “catastrophe” KNOW THIS TERM
↑ GTP- tubulin will “rescue” the MT → continued growth |
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Term
| On what end to alpha beta dimers of tubulin add? |
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Definition
+
especially before GTP hydrolsyis. |
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Term
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Definition
This occurs on the + end
If hydrolysis catches up with dimer addition, MT will shrink = “catastrophe” |
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Term
| β-tubulin hydrolyses what to what? |
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Definition
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Term
| How can we fix catastrophe? |
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Definition
| ↑ GTP- tubulin will “rescue” the MT → continued growth |
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Term
What are the difference configurations of MT?
Describe what singlets, doulets, and triplets are used for. |
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Definition
Singlets =13 protofilaments = MT (25nm diameter)
Protofilament = single vertical column of tubulin dimers
Singlets : carry & move vesicles, organelles, chromosomes
Doublets : make up cilia & flagella - axoneme (motility)
Triplets : make up centrioles & basal bodies (MTOCs) = 9 triplets |
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Term
| Give examples of microtubule directionality |
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Definition
(-) ends = anchored in MTOC (which is a centriole)
For cilia and flagella which uses a basal body as the MTOC
(-) ends = near nucleus, microtubules radiate outward towards cell periphery
Microtubules grow, or shrink by tubulin dimers (alpha and beta) |
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Term
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Definition
| carries material towards (+) end (anterograde) (A for AWAY from the MTOC) |
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Term
| What do Dynein proteins do? |
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Definition
| carries material towards (-) end (retrograde) (back TOWARDS the MTOC |
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Term
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Definition
γ-tubulin = scaffold for growth in the microtubule organising centers (MTOCs); centrosome, basal body (basal body ONLY for cilia and flagella)
Gamma tubulin forms a RING COMPLEX to which alpha tubulin attaches
Microtubules radiate from the MTOC
(-) end attached to a microtubular organising center (MTOC) |
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Term
| Are all MTOCs found in the center of the cell? |
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Definition
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Term
| What is the pericentriolar material for? |
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Definition
| Centrioles organise / make pericentriolar material (anchors & caps MT - end) |
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Term
| How do the MTs grow from the sphere |
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Definition
MTs grow from γ-tubulin ring complexes in the sphere surrounding centrioles (pericentriolar material)
The rind complez is the nucleating site |
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Term
| Describe MTOCs in cilia/flagella |
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Definition
| Basal bodies = MTOCs under cilia and flagella |
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Term
| Describe the make-up of a MTOC Centrosome. |
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Definition
There are two centrioles
A centrosome matrix
AND
9 triplets!
Make pericentriolar material, are at 90 degree angles to each other |
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Term
| What is pericentriolar material |
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Definition
| (anchors & caps MT - end) |
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Term
| MTOC stands for what and what does it contain? |
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Definition
Microtubule Organising center
Centrioles = short cylinders,
9x triplet MTs connected together by radial spokes
Contains γ-tubulin |
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Term
| List where and in what form an MTOC can be found... |
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Definition
Basal body: cilia & flagella (IMP)
Centrosome in interphase cell
Spindle poles: mitotic spindle of
dividing cell
Nerve cell
Centrosome in migrating cell |
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Term
| Why do we need microtubule motor proteins? |
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Definition
Intracellular transport system
Why? Nutritive support! Need to deliver cargo somehow!!! |
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Term
| Describe the directions which the motor proteins take. |
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Definition
Kinesin- goes to + end, anterograde
Dynein- goes back to – end, retrograde |
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Term
| What is the exception to microtubule motors? |
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Definition
Dendrites are an exception to the rule, + ends are located where – end would normally be.
Instead of Kinesin Bringing away it goes towards soma |
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Term
| Is the directionality of kinesins and dyenins universal? |
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Definition
NO,
Instead of Kinesin Bringing away it goes towards soma
Dendrites are an exception to the rule, + ends are located where – end would normally be. |
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Term
| Is movement of motor protein ATP depedent? |
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Definition
Binding of motor to the MT releases ADP. ATP binds activating other motor head to bind. Continuous exchange of ATP hydrolysis to move each head long…very expensive for the cell! Now you can make a connection- lack of ATP, lack of vesicular and nutritive movement within the cell- major issues…
ATP driven: 2 ATPase heads |
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Term
| How NTs travel from cell body (where made), to axon terminal (synapse) |
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Definition
Axons carry impulses from the cell body
Microtubules oriented in one direction
Kinesin (Anterograde)
Dynein (Retrograde)
Lots of ATP!!! |
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Term
| What is the Dynactin Complex? |
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Definition
| Dynactin complex is an adaptor protein that allows the dynein to bind vesicles and bring them into the cell body |
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Term
| How do viruses "hide" in the nervous system? |
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Definition
Transported by retrograde action of dynein (evades BBB)
(Herpes virus, Rabies virus, West Nile virus) |
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Term
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Definition
| Microtubule associated proteins |
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Term
| What is the function of MAPs? |
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Definition
Maps STABILIZE the microtubules;
Catastrophe factors assist in breakdown of the MT. More stable so result is longer, less dynamic MTs
The frequency of catastropes is supressed and/or growth rate enhanced. |
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Term
| How do MAPs protect from MT disassembly? |
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Definition
Inhibit tubulin dissociation (tau)
Link MTs together & to other
cell structures |
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Term
| What are the two domains? |
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Definition
2 tubulin binding domains (stabilises microtubule)
or
1 tubulin binding domain & 1 binding domain to other cellular structures (anchors microtubule in a particular location) |
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Term
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Definition
A centriole is a barrel-shaped cell structure; The walls of each centriole are usually composed of nine triplets of microtubules. This is where the kinetechores come from.
Centrioles act as anchoring sites for proteins that in turn anchor microtubules within centrosomes, one type of microtubule organizing center (MTOC). |
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Term
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Definition
A basal body is an organelle formed from a centriole, and a short cylindrical array of microtubules.
Basal bodies are specifically the bases for cilia and flagella that extend out of the cell. |
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Term
| What is special about thee gamma tubulin ring complexes? |
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Definition
| MTs grow from here and this is the sphere that surronds centrioles. |
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Term
| What is pericentriolar material? |
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Definition
| Pericentriolar material (PCM) is an amorphous mass of protein which makes up the part of the centrosome that surrounds the two centrioles. The PCM contains proteins responsible for microtubule nucleation and anchoring[1] including γ-tubulin, pericentrin and ninein. |
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Term
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Definition
| MTOCs under cilia and flagella |
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Term
| Are all microtubules that grow from a centrosome capped? Are these stable or unstable? Where are the MTOCs Found |
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Definition
| No; the capped ones are stable; MTOCS are not always found in the center of the cell. |
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Term
| What kind of state are dimers added in? |
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Definition
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Term
| Whats the method of how the MT motors work? |
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Definition
| Binding of motor to the MT releases ADP. ATP binds activating other motor head to bind. Continuous exchange of ATP hydrolysis to move each head long…very expensive for the cell! Now you can make a connection- lack of ATP, lack of vesicular and nutritive movement within the cell- major issues… |
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Term
| When it comes to nerve cell transport? |
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Definition
NTs travel from the cell body where they are made to the axon synapse.
This uses a lot of ATP!! |
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Term
| What is the function of catastrophe factor (kinesin 13)? |
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Definition
Catastrophic factor Kinesin 13 increased frequncy of these events so we result in have shorter, more dynamic microtubules.
The frequency of catastrophes is increased. |
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Term
What is the function of MAPs?
How does it do this?
What are the domains for MAPs to carry out their functions? |
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Definition
Protect from MT disassembly by inhibiting tubulin dissociation (tau)
How does it do this?
By linking MTs together & to other
cell structures
Domains?
2 tubulin binding domains (stabilises microtubule)
or
1 tubulin binding domain & 1 binding domain to other cellular structures (anchors microtubule in a particular location) |
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Term
| What is the primary marker of Alzheimer's Disease? |
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Definition
Neurofibrillary Tangles (NFTs) are aggregates of hyperphosphorylation tau.
Hyperphosphorylation means that it disassembles from the MT, MT gets broken down, and form tangles- that interfere with transport) |
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Term
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Definition
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Term
| In Alzheimer disease what happens? |
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Definition
The result:
Forms NFTs
↓ functional MT (depolymerisation & disruption of axon transport) |
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Term
| How do β-amyloid / senile plaques (extracellular)form? What happens to BAPP? |
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Definition
BAPP is beta-amyloid precursor protein
BAPP gets cleaved inappropriately to make plaques.
Then you will get accumulation of β-amyloid peptide (β-A42/43) , apoE also present → progressive neuronal damage. |
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Term
| In Alzheimers, why do Neurofibrillary tangles (intraneuronal)form? |
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Definition
tau (MAP) becomes hyperphosphorylated
Forms NFTs & accumulates in βA plaques
Microtubule depolymerisation & disruption of axon transport |
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Term
| In Alzheimer disease: β-amyloid plaques are incorrectly cleaved where? |
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Definition
| If cleaved at abnormal length (by beta secretase) you get aggregation and then they form fibrils |
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Term
| What proteins are involved in the early onset (<60) of Alzheimers? |
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Definition
Presenile
Presinilin 1
Presinilin 2
β-amyloid precursor -(trisomy 21)
*So, if you have one of these mutations, you WILL get alzheimers
Presinilin 1 and 2 are the names of the secretases (alpha, beta, gamma). The precursor protein is ON chromosome 21, this is why people with Down’s Syndrome are at a higher risk to get alzheimers (think back to block one!) |
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Term
| What proteins are involved in the late onset (>60) of Alzheimers? |
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Definition
Senile
Apolipoprotein E (ε4 allele)
Late onset = Multifactorial (other things besides genes too)
Progressive degeneration of cerebral cortex → dementia |
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Term
| What role does Apo E4 play in Alzheimers disease? |
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Definition
earlier age of onset of LATE ONSET AD
also earlier age of onset in early onset autosomal dominant disease
Apo E2: reduced risk
1 allele ApoE4 : RR 3 (3x risk)
2 alleles ApoE4 : RR 15 (15x risk) + earlier onset of late onset AD) |
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Term
| What is Familial MND And ALS |
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Definition
Familial motor neuron disease (Dynactin subunit)
Familial amyotrophic lateral sclerosis (SOD1)
Lou Gehrigs Disease |
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Term
In Familial MND & ALS you have:
destruction of lower motor neurons
Muscular atrophy, weakness
Destruction of upper motor neurons |
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Definition
| Hyperreflexia, spasticity |
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Term
| When do Centrioles replicate |
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Definition
| before mitosis → spindle poles |
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Term
Describe the three types of microtubles?
1. astral
2. kinetechore
3. polar |
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Definition
ASTRAL--> radiat out of MTOC, organized by pericentriolar material with Gamma-tubulin
POLAR--> Kinesin, push poles apart
KINETOCHORE--> Dynein, pulls sister chromatids to MTOCs |
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Term
| What MT and what protein pushes centrosomal poles apart and why? |
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Definition
| Kinesin MT motors on polar MTs push them apart, elongates the spindle; pushes poles apart --> prep for cytokinesis |
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Term
| Describe the reorganization of MTs during mitosis and what happens in prophase and metaphase. |
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Definition
| Prophase --> Initiate mitotic spindle Metaphase --> mitotic spindle complete, nuclear envelope disappears |
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Term
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Definition
It is the Cytoskeletal structure in cilia & flagella.
9x2 + 2 arrangement...this means:
its outer cylinder is in doublet form and it has two MTs singlets in the center.
Axoneme’s MTOC = Basal body
ONLINE:
the central core of a cilium or flagellum, consisting of a central pair of filaments surrounded by nine other pairs. |
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Term
| What is the structure of a MT? |
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Definition
Its made up of 13 protofilaments.
A protofilament is a long string of repeating alpha and beta tubulin dimers. |
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Term
| Describe how the basal body is formed. |
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Definition
| The complete (13 protofilament) MT grow out of 2 of the 3 MTs in the nine triplets of the basal body (similar to centriole in structure) |
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Term
| There is an inner and outer dynein arms. The outer arm is on one of the doublets. What does it walk on? |
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Definition
| Outer dynein arm walks along adjacent MT doublet |
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Term
| Describe the power stroke. |
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Definition
| Dynein arms slide the outer microtubule doublets relative to one another → waving motion of cilia & flagella |
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Term
| What causes the cilia and flagella bending? |
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Definition
With ATP Dynein walks towards the - end of the adjacent MT doublet.
LINKING PROTEINS attach the adjacent doublets-->get bending (POWER STROKE) |
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Term
| What is Primary Ciliary Dyskinesia (PCD)? |
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Definition
Mutation in DYNEIN--> NO POWER STROKE
immotile cilia & sperm
→ retention of secretions &
recurrent infection (bronchitis,
otitis media & sinusitus)
→ infertility (sperm, fallopian tubes)
That is Kartagener syndrome. |
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Term
| In PCD (Primary Ciliary Dyskinesia )/ Kartagener syndrome describe the effect of the mutation? |
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Definition
There can be:
Total lack of dynein arms or
Defect of inner dynein arms
Results in → immotility of cilia & sperm
REMEMBER:Mutation in AXONEMAL dynein; nothing wrong with cytoplasmic dynein |
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