Week 3 stuff Flashcards
Regulation of Microtubules
- Microtubule capping proteins
2. Microtubule severing proteins
3 examples of microtubule severing proteins
katanin
spastin
fidgetin
Microtubule functions (4)
- Cellular cytoskeleton
- intracellular transport
- cell division
- cilia
Microtubules in cell division (3)
astral microtubules
kinetochore microtubules
centrospindle- overlapping attachment
Domains of microtubules
alpha, beta, and gamma
Plus end Subunit
beta
minus end subunit
alpha
GTP cap function
Stabilization
Microtubule organizing center
centrosome
Each centrosome contains 2 ___
centrioles
Gamma tubulin forms _____ which binds to ____
rings outside of centriole
binds to minus ends
Kinesin homodimer
Kinesin I
Kinesin heterodimer
Kinesin II
N terminus of kinesin
head domain
C terminus of kinesin
tail domain
for the tail domain to bind to cargo there is usually an associated ____
adaptor protein
Energy used in kinesins
ATP
Retrograde transport of ___ is essential for neuron proliferation
NGF
In neuropathies, damage to the forward pathway is typically ____ than damages to the retrograde pathway
less severe
Actin energy
ATP
Minus end of actin has ____
open ATP pocket
Actin step needed to grow
nucleation
Actin filament structure and regulation (4)
- G actin concentration
- ADP to ATP exchange
- Capping
- Depolymerization/severing
2 proteins that regulate nucleation
Formin (FH2)
Arp2/3
Arp2/3
branched
FH2
bundles
Arp2/3 and FH2 initiate nucleation by forming _____
pseudonucleation centers
Formin activation
small GTPases bind and activate
Actin roles in cell function
- epithelial cell polarity
- contraction
- cell motility
- cell division
Tight Junctions (TJ)
Separate apical and basolateral
Microvilli-> ___ dependent
FH2
Myosin involved in transport
Unconventional myosins
Cell motility: Arp2/3 complex regulates ____ formaion
lamellipodia
______ complex regulates lemellipodia formation
Arp2/3
Formins complex regulate ____ formation
filopodia
_____ regulate filopodia formation
Formins complex
Function of intermediate filaments
mechanical stability
receptor lipophilic
can be intracellular
receptor hydrophilic
has to be on cell surface
cell storage- lipophilic
NO
cell storage- hydrophilic
yes in vesicles
control of release lipophilic
only by synthesis
speed lipophilic
slow
speed hydrophilic
fast
Receptor types (4)
- Ligand (or voltage) gated ion channels
- GPCRs
- Enzyme linked receptors
- Nucleat receptors- TFs activated by cell penetrating signaling molecules
Second messenger examples (5)
- Ca2+
- cAMP
- IP3
- DAG
- NO
cAMP is generated by ___
Adenylate cyclase (AC)
DAG are generated by ___
Phospholipase C (PLC)
NO generated by ____
NOS
Signaling proteins, activated by receptors or second messengers, can activate other signaling or effector proteins (including enzymes that generate second messengers) in a variety of ways. Including:
protein modification
protein-protein binding
Amplification often depends on _____
how many downstream targets affected
time it takes to terminate activity of a signaling molecule
signaling- Node
multiple input/multiple outputs
signaling- module
groups that function together
PDE5 function
breaks down cyclic GMP to GMP
PDE5 binding
catalytic site and noncatalytic site
cooperative binding
Protein that phosphorylates PDE5
PKG
PDE5 inhibitor
Sildenafil (Viagra)
binds to catalytic site
Receptor tyrosine kinase activation is driven by _____
ligand mediated dimerization
Key downstream activation of EGFR
Ras
Active Ras
Ras-GTP
Inactive Ras
Ras GDP
GTP->GDP
GAP
GDP->GTP
GEF
Adaptor protein involved in Ras activation
Grb2
Domains of Grb2
SH2 and SH3 domains
SH2 domain of Grb2 binds____
Phospho-Tyr containing peptides
SH3 domain of Grb2 binds ____
Pro-containing peptides (Sos)
Ras GEF involved in Ras activation
Sos
Recruitment of Sos to the receptor ____
brings Sos in close proximity with Ras which is sequestered at the cell membrane
Two ways to inhibit EGFR
- small molecule inhibitors that bind kinase domain
2. antibodies that bind extracellular domain
Example of antibody that blocks ligand binding site
cetuximab
Example of small molecule inhibitor of EGFR
getfitinib
What part of EGFR does getfitinib inhibit
ATP binding domain
Mutant EGFR is more active and more potently inhibited by ____
getfitinib