Chapter 3 Flashcards
what is induction? what is compentence?
induction: close range interaction of different types of cells
competence: ability to respond to specific inductive signal
what is Hans Spemann do?
transplanted frog gastrula ectoderm cells into newt gastrula
- they ended up switching mouths
- proved that induction tells them what to do, but not how to do it (genes encode for that)
what is juxtacrine signaling? what are three examples
direct contact b/w the inducing & responding cells
- delta-notch, cadherins, integral MB ligands
what are cadherins?
calcium dependent, transmembrane integral protein that attaches to a cytoskeleton
cells that are the most sticky (more surface tension) are in the middle
creates a hierarchy of cell types based on surface tension
endocrine vs paracrine?
endocrine: hormones via bloodstream, long-distance
paracrine: short-distance, diffuses into ECM
what are morphogens?
a type of inducing paracrine that creates cell pattern & form
describe how paracrines form a gradient
little to no paracrine signal = no response
medium signal = response #1
large signal = response #7
- cells nearby get a large dose, those further away get a small dose and produce a different response
what are the four families of paracrines?
FGF (fibroblast growth factor)
hh (hedgehog)
Wnt (wingless)
TGF-beta (transforming growth factor)
what does FGF do?
development & tissue maintenance
- makes limbs grow longer
what does hedgehog do?
orientates cells in relation to other cells
- anterior (pinky) & posterior (thumb)
- dependent on a gradient of HH signal
what does Wnt do?
establishes polarity
- communicates which cells get FGF & hedgehog
what does TGF-beta do?
regulates ECM
- differentiation b/w cell types
describe the general way signal transduction works?
paracrine binds and induces activation of proteins
what type of paracrine uses RTK? (receptor tyrosine kinases)
FGF (fibroblast growth factor)
describe the RTK pathway
- ligand / paracrine binds RTK receptor
- receptor dimerizes
- autophosphorylation of receptor & tyrosine residues
- adaptor protein
- GNRP
- Ras becomes active –> RasGTP
- Raf
- MEK
- ERK, enters nucleus
- TFs activate (Mift)
- transcription occurs
describe the canonical Wnt pathway
- Wnt (ligand) binds to frizzled protein (receptor)
- disheveled
- blocks GSK-3 inhibitor
- frees beta-catenin & it accumulates (no phosphorylation)
- goes inside nucleus & binds to LEF/TCF
- transcription occurs
what is ubiquitin and how does it relate to the canonical Wnt pathway?
ubiquitin
- tag put on cells to be degraded by the proteasome
- phosphorylation of beta-catenin by GSK-3 causes ubiquitin to bind
- causes beta-catenin to be degraded
what are the layers in the ECM (extracellular matrix) and how does it regulate paracrines?
epithelium, basal lamina, collagen
fibronectin = long, EXM molecule, “road”
integrins = span from ECM to intracellular matrix
- integrate things from ECM (signal carried inside from outside)
what is anoikis and how does this ECM function regulate paracrines?
death upon detachment from ECM
- occurs if integrin detaches from fibronectin matrix, it can no longer function
what is the function of Bcl-2 & Bcl-XL?
they inhibit apoptosis when activated
how can Bcl-2 & Bcl-XL start apoptosis? what is the pathway?
must be inhibited by Bik or Bax
- active Bik/Bax inhibits Bcl-2
- activates Apaf 1
- caspase-9 cleaves off inhibitory region of caspase-3 to initiate apoptosis
what happens to apoptosis if the alternative splice site of Bcl, Bcl-XS, is activated?
it is unable to inhibit Apaf 1, so apoptosis occurs
what are caspases?
starts off as a zymogen (what it’s called before activation) that has an inhibitory region
- once the inhibitory region is cleaved, the caspase is activated
RELEASE THE BEAST
what is meant by maintaining differentiation?
I am a muscle cells, now I need to stay a muscle cell
what are the four ways cells can maintain differentiation?
- autoregulation via TFs
- promoter stabilization
- autoregulation via autocrine signaling loop
- paracrine signaling loop
describe autoregulation via TFs
the gene gets activated & produces a TF that activates the gene again
- all occurs intracellularly, TFs bind to two different enhancers on the same gene
describe promoter stabilization
protein binds to promoter (ex: trithorax) & prevents nucleosome formation so it is always active, always unwound
describe autoregulation via autocrine signaling loop
gene releases a ligand molecule that binds to it’s own receptor outside cell
- receptor keep activating the gene, which causes the release of another ligand that the gene is activated by
describe paracrine signaling loop
two nearby cells exchange & make ligands for each other to keep each other active
what are two stages of commitment to a cell type? describe them
- specification = receives signal
- when removed, it will still differentiate, but new signals can change fate - determination = starts to do signal, maintenance processes start
- new signals cannot change fate
