Cytoskeleton Flashcards
What are three kinds of protein structures that make up the cytoskeleton?
> microfilaments
intermediate filaments
microtubules.
What are features of actin filaments?
highly conserved structure, filaments organize into bundles, bind to transmembrane proteins, exist as monomers (G-actin) or long chains (F-actin).
What does G actin have a binding site for?
> ATP (binds tightly to G-actin)
How many other monomers can a single actin monomer bind with?
2
Do actin monomers display polarity?
yes
What is nucleation?
> The first step of actin polymerization.
> A trimer is formed and additional actin monomers can then be added to either end.
ATP-actin associates which end of the actin filament?
> the plus/barbed end
> ADP is made once actin binds here.
What affects the rate of monomer addition to a growing filament?
the cytosolic concentration of actin monomers.
Which end of the actin filament grows faster?
barbed end
At what concentration do actin filaments disassemble?
low concentrations of G-actin
What is treadmilling?
> intermediate concentrations of G-actin
AND
> a dynamic equilibrium of growth and recession at the barbed and pointed ends.
What do high concentrations of G-actin favor?
higher concentrations of G-actin at both ends (e.g. growth)
What do cytochalasins do?
bind to barbed ends and prevent more actin monomers from binding. They also prevent movement/cell division.
What does phalloidin do?
> binds to actin filaments and prevents dissociation.
> can be labeled with fluorescent dyes to allow visualization of actin filaments
What determines the diversity of functions of actin?
the actin-binding proteins, not actin itself.
What are some actin binding proteins?
spectrin (RBC passage through capilliaries); dystrhophin (binds cytoskeleton to plasma membrane); villin/fimbrin (holds actin filaments together); calmodulin and myosin I (cross links actin to plasma membrane).
What actin-binding proteins control treadmilling?
thymosin and profilin. Both prevent actin from being polymerized.
What are intermediate filaments?
filaments that provide tensile strength in neurons and muscle, strengthen epithelial cells as desmosomes and hemidesmosomes, etc.
What is the structure of intermediate filaments?
> monomer consisting of a central alpha-helical rod flanked by head and tail domains.
How are intermediate filaments assembled?
two polypeptides form a dimer —-> dimers form tetramers —-> tetramers form protofilaments —-> 8 protofilaments form a filament.
What are the functions of intermediate filaments?
> form cytoplasmic networks in cells
> associate with other cytoskeletal elements to form a scaffolding that organizes the internal structure of the cell.
What are microtubules made of?
tubulin dimers; there is an alpha and beta subunit that make two separate helices.
What is dynamic instability?
alternate phases of slow growth and rapid depolymerization. GDP is quickly released from the - end.
What is colchine?
a drug that inhibits microtubule polymerization. It is used for cancer treatment.
What is taxol?
an anti-cancer drug that stabilized molecules (prevents depolymerization).
What are some functions of the cytoskeleton?
> cell movement > support and strength > phagocytosis > mitotic spindle formation > cytokinesis > changes in cell shape. > cell-to-cell and cell-to-extracellular matrix adherences
What molecule travels from the minus end to plus end to deposit tubulin?
kinesin
Which molecule carries cargo from the plus end to the minus end?
cytoplasmic dynein.
Which myosin molecule is the only one with two heads?
myosin I
What do the heads of kinesin and cytoplasmic dynein bind to?
microtubules
What do the heads of myosin I and II bind to?
actin
What do the tails of kinesin and cytoplasmic dynein bind to?
vesicles
What do the tails of myosin I and II bind to?
the cell membrane (I) and myosin II (II).
Is actin polymerization reversible?
> yes
_____-actin dissociates more readily from filaments than _____-actin?
> ADP
> ATP
Actin fact
> actin is a very common and very ubiquitous protein found in all cells, but in spite of the fact that it has pretty much the same structure in all cells, it is involved in a number of kinds of functions
This is determined by the actin-binding proteins and not by actin itself?
> the diversity of function of actin filaments
Spectrin (ABP)?
> found in RBCs
> binds cytoskeleton to plasma membrane
Dystrophin (ABP)?
> binds cortical cytoskeleton to the plasma membrane
Villin and Fimbrin (ABPs)?
> cross-link actin to plasma membrane in microvilli
alpha-actinin (ABP)?
> cross-links stress fibers and connects actin to protein plasma membrane complex complexes
Filamin (ABP)?
> cross-links actin at wide angles to form screen like gels
Thymosin (actin-binding molecule/control treadmilling)
> captures actin monomers
> prevents monomers from being polymerized
Profiln (actin-binding molecule/ control treadmilling)
> binds to actin monomers and prevents monomers form being polymerized
> facilitates exchange of ADP for ATP—-which favors polymerization
> only ATP-actin monomers can be assembled into F-actin
Gelsolin (actin-binding molecule/ control treadmilling)
> destabilizes F-actin and caps actin filaments, preventing loss and addition of G-actin
In presence of calcium ion, fragments actin filament and remains bound to plus (+) end
Cofilin (actin-binding molecule/ control treadmilling)
> triggers depolymerization of ADP-bound actin at minus end
Arp2/3 (actin-binding molecule/ control treadmilling)
> initiates growth of F-action from sides of existing filament—causes branching
Phalloidin (actin-binding molecule/ control treadmilling)
> prevents depolymerization by binding to actin filaments
Latrunculins (actin-binding molecule/ control treadmilling)
> binds to G-actin and induces F-actin depolymerization
These intermediate filament types are associated with keratin?
> type I
» acidic keratins
> type II
» neutral to basic keratins
Microtubules consist of _____ protofilaments arranged parallel to form a cylinder with a hollow core?
> 13
Protofilaments have a ______ growing plus (+) end and a _____ growing minus(-) end?
> fast
> slow
What type of tubulin dimers associate with the growing end of microtubules?
> tubulin dimers with GTP bound to the beta-tubulin
Low calcium ion concentration causes this end of the microtubule to grow faster than the other?
> Plus (+) end grows more rapidly than minus (-) end
At high concentrations of _______, the dimers are added more rapidly than GTP is hydrolyzed, and the microtubule grows?
> tubulin-GTP
Drugs that inhibit microtubule polymerization?
> colchicines
colcemid
vincristine
vinblastine
This drug is used to treat Hodgkin’s Lymphoma?
> vinblastine
Drugs that stabilize microtubules?
> taxol
This drug is used to treat breast cancer?
> taxol
How do drugs such as colchicine work to prevent polymerization of microtubules?
> by binding to the tubulin dimers and preventing their assembly into microtubules
How do drugs such as taxol work to stabilize microtubules?
> binds to microtubules preventing their depolymerization
taxol disrupts mitosis by affecting the dynamic assembly of the mitotic spindle.
antimitotic drugs bind to reverse sites on tubulin, and
What mediates the anterograde transport of cargos along microtubule?
> kinesin
What mediates the anterograde transport of cargos along microtubules?
> cytoplasmic dynein
This may provide a mechanism for the transport of multiple cargos along microtubules?
> raft protein complex
