DSA 4 Cytoskeleton Flashcards
Components of the cytoskeleton
filamentous proteins (microfilament (actin), microtubules, intermediate filments (not covered here
accessory proteins,
motor proteins, like myosins(actin motor protein), kinesins and dyneins (microtubule)
characteristics of actin filaments (microfilaments)
most ubiquitous cytoskeletal protein in most cells is actin.
Polymerization of actin protein monomers(G-actin) creates thin ,flexible filaments (F-actin)
InF-actin, individualG-actin molecules are always oriented in the same direction relative to one another consequently, F-actin is polar. F-actin has two ends:
– Faster-growing “barbed end” (plus end).
– Slower-growing “pointed end” (minus end).
fuction of microfilaments in cell
benneath the plasma membrane actin filaments make a newtwork that supports, shapes, allows cells to migrate, engulf particles and devide
what are the actin associated proteins
Actin-binding proteins control actin filament polymerization, depolarization, and stability. Formin and the Arp2/3 complex are the main actin filament-initiation and elongation proteins
Formins: nucleate the actin monomer polymerization by binding ATP-actin. Moving down the developing filament, they add monomers to the plus end. Thus, formins is responsible for the linear unbranched actin filament initiation and elongation.
Arp2/3, drives the elongation of branching actin filaments, which are essential for cell migration/movement. The Arp2/3 proteins bind ATP- actin at filament plus ends to form a new branch. Once branching begins, Arp2/3 will remain at the branch base adjacent to the branch minus end. Mutation of WASp (protein association with Arp2/3) is associated with Wiscott-Aldrich syndrome/
Profilin- binds actin monomers and increases ADP-ATP exchange, increases ATP actin concentration
what are the steps of Actin monomers polymerization
- nucleation- 3 actins join
- addition of actin on both sides : - end had ADP bound actin while the + end has ATP actin bound. then grows much faster at + end, but ATP not needed for growth but happens fater
- Treadmiling (special to actin); when ATP actin added is equal to the ADP actin disassociating.
Formins:
Formins: nucleate the actin monomer polymerization by binding ATP-actin. Moving down the developing filament, they add monomers to the plus end. Thus, formins is responsible for the linear unbranched actin filament initiation and elongation.
Arp 2/3
drives the elongation of branching actin filaments, which are essential for cell migration/movement.
The Arp2/3 proteins bind ATP- actin at filament plus ends to form a new branch. Once branching begins, Arp2/3 will remain at the branch base adjacent to the branch minus end. Mutation of WASp (protein association with Arp2/3) is associated with Wiscott-Aldrich syndrome/
Profilin
another actin-binding protein, binds actin monomers and increases ADP-ATP exchange. This boosts local ATP-actin concentration and actin polymerization.
Wiscott-Aldrich Syndrome
muatation
Malepatientswithdefectsinproteinsthat activate the Arp2/3 complex, a protein of the Wiskott-Aldrich syndrome protein (WASP) family.
xlinked
Signsandsymptoms
– Recurrent respiratory infections (because
of hereditary immunodeficiency),
– Thrombocytopenia (low platelet count) present from birth on
– Eczema of the skin after the first month of life.
________is another actin associated protein
in skeletal muscle
tropomyosin
in skeletal muscle
protect and stabalize actin
________is another actin associated protein
for remodeling
cofilin can remodel or modify actin
generates new ends depol or pol after breaking the original
cell motility or division
____ and _____ associated actin proteins that bind the membrane
structural bases
Spectrin (major contributor in RBC) and ankryn (anchor for spectrin
defect in hereditary spherocytosis
affected individuals symptoms
RBCsare round (spherocytes) instead of concave. It results from
* Mutationsof ankyrin-1 ,resultinanankyrin-1protein
that does not bind the RBC membrane and is therefore
unavailable for spectrin binding.
* MutationsofSPTB(spectrinbeta)resultinaltered
spectrin that cannot associate correctly with actin in the RBC membrane.
anemia and jaundice
_____ is another actin associated protein present in muscles
Dystrophin in muscles cellls
stabalizes sarcolemma
- It stabilizes the sarcolemma(plasma membrane of the muscle cell) during the stress of muscle contraction by maintaining a link between the cytoskeleton and the extracellular matrix.
- When dystrophinis absent, the sarcolemma is disrupted, allowing unregulated calcium entry, which causes necrosis of the muscle fiber.
defect in Duchenne’s muscular dystrophy, an X- linked recessive condition.
and Becker
by A deficiency in dystrophin
X- linked recessive condition
Duchenne’s starts in early childhood – deletion with frameshift mutation
Becker slowly progressive -delition
_____ are another actin related protein
what are the different types
myosins
F-actin inhibitors
Cytochalasins
– Bind to the barded end preventing further addition of G-actin. – Produced by fungi
Phalloidin
– binds to F-actin preventing depolymerization.
– Produced by the Death cap mushroom Amanita phalloides.
Latrunculins
– disrupt F-actin by binding to G-actin and inducing directly F-actin depolymerization. – Derive from Red Sea sponge Lantrunculia magnifica
microtubule structure and characteristics
heterodimers.
– α-tubulin bound to GTP
– β-tubulin bound to GTP
γ-tubulin is third type of tubulin which is concentrated in the centrosome, where it plays a critical role in initiating microtubule assembly
Polarized, with plus end which grows more rapidly than the minus end.
The tubulin subunits bind GTP
Unlike microfilaments undergo alternate phases of slow growth and rapid depolymerization i.e., dynamic instability.
fuctions of microtubule
They function to determine cell shape and participate in a variety of cell movements, including some forms of cell locomotion, the intracellular transport of organelles, and the separation of chromosomes during mitosis.
describe Polymerization of microtubules and dynamic instability
GTP binds to α- and β-tubulin, similar to ATP binding to actin, to regulate polymerization. Specifically, microtubule development involves adding GTP-bound tubulin dimers to the plus end.
GTP bound to β-tubulin (but not α-
tubulin) is hydrolyzed to GDP immediately after polymerization. GTP hydrolysis lowers tubulin dimer binding affinity, causing GDP-bound tubulin to dissociate from microtubule ends rapidly.
To prevent fast depolymerization, cells must anchor microtubule minus ends in the centrosome or microtubule organizing center.
Dynamic instability occurs when fast GTP hydrolysis at the plus end causes microtubules stabilized at the minus end to alternate between growth and shrinking
what are the microtubule associated proteins (MAPs)? (5)
The microtubule organizing center (MTOC) or centrosome stabilizes microtubule minus ends in cilia and flagella
- Polymerases increase GTP-bound tubulin incorporation to promote growth.
- Depolymerases dissociates GTP-bound tubulin from the plus end, shrinking microtubules.
- Tau protein
-MAP2
-CAP
What are the fuctions of
- Tau protein
-MAP2
-CAP
- Tau protein is a MAP protein stabilizes neuronal axon microtubules (tau protein is not present in dendrites) Modifications of tau protein including phosphorylation, acetylation, and ubiquitination has been associated with Alzheimer disease. Tau protein is specific to axonal microtubules.
- MAP2 is a MAP protein stabilizes neuronal dendritic microtubules. It functions similar to Tau in terms of stabilizing the microtubules.
- Cap proteins are MAPs that stabilizes both ends of dendritic and axonal microtubules because these microtubules are not connected to MOTC.
microtubule targeting agents
Chochicine
vicristine and vinblastine
Maytansine
Taxol
(Coach May Taxis Vinyards)
Coalchicine
inserts between the components of α/β- tubulin dimers and prevents its assembly into the plus end of microtubule.
Vincristine and vinblastine
Vincristine and vinblastine occupy a space between adjacent α/β-tubulin heterodimers.
Maytansine
Maytansine binds to β-tubulin at the plus end thus inhibiting filament prolongation.
Taxol (ex. Paclitaxil)
binds to along microtubules to β-tubulin stabilizing them in polymerization state thus preventing their depolymerization.
what proteins are responsible for carrying cargo in microtubules? and how do they work ?
Kinesin I and Dyneins (use ATP hydrolysis for energy of transportation)
Kinesin I: transports cargo towards the plus end (from center to periphery of cell) of microtubules, near the plasma membrane or cortex of cell
-transport NT along the aconal MT towards synaptic cleft
Dyneins: mediate transport towards the minus end of microtubules, facing the centrosome in the middle of cell (from periphery to the nucleus )
viruses that use Dyneins to transport themselves into the cell’s cell body
Clostridium tetani, herpes simplex, poliovirus, rabies virus
rabi costa tetas por herpes
centrosomes
