Exam 2 Flashcards
microtubules
tubulin dimers of alpha and beta tubulin –> 13 protofilaments
tubulin is a
GTPase
+/- end of microtubules
+ end: high exchange rate of alpha and beta tubulin - end: static end
functions of Microtubules
mitotic spindle, organelle transport, cell shape
dynamic instability in microtubules
catastrophe = shrink, rescue = grow
microtubule associated motor proteins
- dyenin (- end directed) 2. kinesin (+ end directed)
centrosome
MT ognizing center/site of nucleation (genesis of cytoskeletal polymer) - uses gamma tubulin
basal body
MT organizing center for cilia and flagella
axonemone
9+2 microtubule structure of cilia and flagella *dyenin drives axenemal activity
immotile cilia syndrome
defect in anexome structure –> obtrusive lung disease, male sterility
kartagene’s syndrome
situs inversus and immotile cilia cyndrome
lissencephaly
mutations in microtubule proteins HS1 and doublecortin
Charcot-Marie-Tooth
kinesin mutation
microfilaments
nonhollow polymers of actin with ATPase activity
ends of microfilaments are called
barbed end (+) and pointed end (-) **myosin moves towards the + end
hereditary spherocytosis
RBC forms spherocyte because weak binding of spectrin to band 4
epidermis bullose simplex
intermediate filament disorder - keratin mutation in basal skin cell layer, results in very sensitive skin that easily is torn
progeria (hutchinson gilford syndrome)
intermediate filament disorder - “fast again” mutation in nuclear lamin protein autosomal dominant
Most cells in our bodies are in what phase?
G0
CDKs control cell cycle progression by activating
cyclins
p54
induces cell cycle arrest by inhibiting CDKs - can also trigger apoptosis
terminally differentiated cells
have permanently exited the cell cycle (so differentiated that they can’t re-enter)
totipotent
cells from the fertilized egg/morula; can become any cell type
pluripotent
cells from the blastula –> can be ecotoderm, mesoderm, and endoderm
multipotent
ex. progenitor hematopoetic cells
unipotent
cells that give rise to a particular cell type
VEGF
for endothelial cell proliferation
stem cell renewal
required to replace differentiated cells
forms of senesence:
- stress induced senescence 2. telomere shortening-induced senescence (replicative) 3. oncogene-induced senescence
telomere shortening induces
p53 and pRb pathway leading to growth arrest and senescence –> facilitate tumor progression
werner syndrom
rare autosomal recessive premature aging single gene WRN (DNA helicase RecQ protein)
paracrine signaling
acts locally
autocrine signaling
cell makes a peptide and is activated by it (inflammation)
scaffold proteins
bring specific proteins together in proximity. they are non-catalytic proteins
tyrosine kinases
associated with activated growth factor receptors; are rapid and transient
ser/thr kinases
longer lasting phosphorylation
phosphorylation is currency of growth factor signaling because it…
is rapid, reversible, and linked to signaling cascade
second messengers
soluble, low MW regulators of signaling proteins; rapid signal amplification
steps of signal transduction
- receptor-ligand binding 2. G protein activation 3. MAPK cascade 4. TF actvation
3 main families of cell surface receptors
- ion channel 2. G protein linked 3. enzyme linked
GEF (guanine nucleotide exchange factor)
facilitates dissoication of GDP from G protein (alpha subunit)
GAP (GTpase activating protein)
stimulates GTP hydrolysis for inactive form of GDP bound to G protein
adenylyl cyclase
large transmembrane protein regulated by G proteins and Ca2+; coupled to Gs; stimulates cAMP which modifies gene expression
receptor desensitization
GRKs (G protein linked receptor kinases) phosphorylate a receptor; arrestin binds and desensitizes via: 1. inactivates receotir through uncoupling 2. acts as adaptor protein to couple receptor to clathrin coated pits for sequestration/degradation of receptor
cholera
toxin gives ADP ribose to alpha subunit of Gs so it can’t hydrolyze GTP –> acitve state –> Cl and water efflux into gut –> diarrhea
steps in enzyme linked receptors
- receptor dimerization 2. autophosphorylation 3. phosphorylation if cytoplasmic signaling proteins
Ras
monomeric GTPase - mutations in it cause cancer
MAPK
ser/thr kinases; usually at end of cascade
PKC steps
- ligand receptor binding via G protein 2. PLC cleaves PIP2 to IP3 and DAG 3. IP3 binds to receptors on the ER and Ca2+ released into cytoplasm 4. DAG is precursor in arachidonic acid generation, and in direct binding/activation of PKC
NFKB
latent gene regulatory proteins that regulate inflammatory repsonses
- heterodimer of 2 related protiens
- inactive when bound to I-KB
I-KB
Binds/sequesters NFKB. When stimulated, releases NF-KB so that it can translocate to the nucleus to stimulate transcription of certain genes
functions of apoptosis
- sculpting/morphogenesis
- deleting unecessary structures
- control cell numbers
- eliminate bad cells
caspase
cysteine protease
initiator caspase
begins the apoptotic process (caspase 8 or 9)
effector caspase
activated by upstream caspase (3, 6 or 7)
cytochrome c
- in intrinsic apoptototic pathway
- released from mitochondria into cytosol
- causes Apaf 1 to oligomerize into apoptosome
- apaf recruits caspase 9
CAD (caspase dependent deoxyribonucleosomes)
inactivated by ICAD (inhibitor); caspase 3 inactivates ICAD so that CAD can cut up the chromosomal DNA between nucleosomes
FLIP
dimerizes with caspase 8 in the DISC (death inducing signaling complex) preventing apoptosis
Bcl-2
regulates intrinsic pathway of apotosis by controlling cytochrome c relase; involved in both pro and anti apoptosis
guardians
prosurvival - bind and inhibit effectors
sensors
proapoptosis - inhibit guardians; can’t kill without effectors; response to environmental cues
effectors
proapoptosis; perturb mito intracellular membranes. need to be primed/activated
bax and bak
respond to cytotoxic signals; confirmational change causes membrane to release apoptotic mediators
