Lecture 4 - Quiz 1 Flashcards
What promotes cell migration (general)?
Cell polarity so there can movement in one direction and cytoskeleton that is dynamic and constantly remodeled - there is a specificity of location of different cytoskeleton fibers for different functions
How is the cytoskeleton regulated?
Cell signaling from the ECM across receptors that pass on to the cytoskeleton which can change organization or movement of organelles, change cell shape
What are some examples of MF based structures?
Very diverse Microvilli, adherens belt contractile ring, motile filopodia, lamellipodium, stress fibers, phagocytosis
How does polymerization of actin occur?
Globular G-actin adds to form filament F-actin by nucelating, elongation, and steady state
What is the lagging phase/rate limiting step of G-actin polymerization?
Nucleation
What are the two classes of actin nucleating proteins?
Formins – lead to assembly of long actin filaments - help to form nucleus, or Arp2/3 complex to form branched networks
What regulates Formins?
When RBD binds to Rho - FH1 and FH2 domains are accessible
What regulates Arp2/3?
ACW sequence binds to Arp2/3 - when RBD binds Cdc42 - ACW and RBD are part of WASp
What toxin binds to the (+) end of F-actin to block further addition?
Cytochalasin D
What toxin sequesters G-actin to inhibit it from adding?
Latrunculin
What toxin enhances nucleating by binding and stabilizing actin dimers - lower the critical concentration?
Jasplakinolide
What toxin binds between F-actin subunits locking adjacent subunits together to prevent depolymerization and can be used for labeling?
Phalloidin
Which actin cross-linking protein makes tight bundles and which makes flexible arms?
Fimbrin - tight, filamin - flexible arms
Which actin cross-linking proteins links PM to actin?
Dystrophin
What does Class I myosin do and what is it’s structure?
It is only one monomer associated with the membrane to perform endocytosis
What is Class II myosin used for?
Muscle contraction - works by sliding across actin to bring Z disks closer together while utilizing ATP and calcium
What is the structure of muscle?
Sarcomeres are the repeating units in myofibrils which make up multinucleated muscle fibers which make up muscles
What controls smooth muscle contraction?
Phosphorylation of myosin by a kinase controlled by calcium to activate myosin
What is Class V myosin used for? And what does it utilize to do work?
Used in organelle transport works by taking steps hand-over-hand with it’s two heads to give 72 nm steps - utilizes ATP - neck domain determines rate of movement
What is chemotaxis? and what signals are used?
When cell senses soluble molecules and follows them along a concentration gradient to their sources - phosphoinositide signals to signal to actin cytoskeleton
How do cells move?
Membrane extended by actin network at leading edge to push membrane forward - PM attaches to substratum by focal adhesions to prevent lamella from retracting (uses integrins) - myosin contraction in rear of cell pushes everything forward - focal adhesions in rear are broken and integrins recycle and tail is brought forward
What coordinates the movement of a cell based off polarity?
GFs
What are actin structures under control of?
Rho family of GTPases
What does Cdc42 do? and what is it activated by?
Activates Par6 for polarity and WASp for Arp2/3 for filopodia formation - also activates Rac - activated by GFs
What does Rac do? and what is it activated by?
Activates WAVE which activates Arp2/3 for lamellipodia formation - activates Rho - activates by GFs and Cdc42
What does Rho do? and what is it activate by?
Activates Rho kinase and formin which lead to stress fiber formation and contraction - activated by LPA and Rac - inhibits Rac
Where in the cell do Cdc42, Rac and Rho interact?
Cdc42 and Rac in the front, Rho in the back
What is the process of invasion-metastasis?
Tumor forms – there is a localized invasion into blood vessels – interaction with other blood components like platelets and lymphocytes – moves through circulation – arrests itself in various organs – extraverts out of blood stream – forms micrometastasis in secondary site – colonizes to form macrometastasis (utilizes transcription factors)
How can metastasis be monitored?
In vitro cell invasion assay with transwell and porous membrane with chemoattractant below - count cells to see how many move, in vivo luciferase tracking by imaging
How does initiation of adaptive immune response occur?
Mature T and B cells delivered to lymph node via circulation –> antigen and antigen laden DCs enter lymph node –> B cells bind antigen and move to B cell follicles –> T cells activated by antigen laden DCs allowing T cells to enter circulation –> activated T cells also interact with B cells leading to B cell differentiation and antibody production
How NK cells show specificty, kill infected cells and what do they secrete?
Inhibited by normal cells, show specificity by utilizing different receptors, kill by using perforin/granzyme and secrete IFN-gamma for anti-viral defense
