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Flashcards in Signaling Pathways and Development Deck (41):
1

Hh and Wnt pathway facts

signally is involve din maintaining stem cell niches in various tissues
-imlicated in cancer and tissue repair
-important for dev
occurs in primary cilium and gets sent down the ciliary shaft

2

uses of indian, soncc, desert hh

dev of bone and cartilage

dev of CNS

dev of peripheral nerves

3

Hh (or any hh variant)

ligand

secreted hydrohphobic proteins that are produced/secreted by localized cell group which they diffuse away from

4

Ptc receptor

Patched

binds hh ligands
-12transmembrane protein with homology to actuarial proton driven transmembrane transporters

5

Smo

Smoothened-no bind Hh ligands-interacts with pt.

-7 alpha hlix g protein coupled transmembrane protein

enter primary cilia

6

gli/ci proteins

gli rep/act

how turned on/off

tfs that either activate or rerpesses hh genes

rep=partially proteolyses protein that functions as transcriptional repressor-represses hh gene

act-full length protein that functions as a transcriptional activator-activates hh gene

phosphorylated to turn off-results in targeting to proteasome after recruit another complex
-alot of phosphorylation

remove phosphates to send to nuc

7

pka

protein kinase a

phosphorylates gli/ci proteins to target them for prteolysis in proteosome

8

regulation of gli/ci protein proteolysis

when smo is activated by ptch- dephosphorylate and activate gli-goes into nucleus

when smo not activated by pitch-gli is phosphorylated and sent to proteasome

9

primary cilla

nonmotile cilia that exist on most cells of vertebrate body

sense ECM info

10

Role of cilia in human function

invovled in hh signalling

localize signal transduction componentes

cilipathies result in vision, hearing, smell. situs inverses, hh signaling, etc

11

IFT proteins

intra flagellar transport

moe cargo along microtubules

maintain iila integrity

link with dynenin=allow movement up and down cilia

12

how use IFT protein for Glirep and GLIact

Rep-PTC inhibits Smo translocation into cilium, IFT proteins shuttle GLIrep into nucleus

Shh blocks pt. allow smooth to translocate into cilium-IFT proteins shuttle glitch into nucleus

13

Congeinital human Hh disorders affect which body parts

limba nd CNS

14

where is shh localized in early developmoent

limb buds/early CNS as organizing centers

lends to development of polarity

15

Organizing centers direct

pattern formation

16

ZPA

what is ZPA morphogen

zone of polarizing activity

proteins made here fuse away
-induce secndary tissue development

Shh

17

Shh knocout mice

cyclopedia-failture oto problery divide eyes into two vanities

holoprosencepahy-one forebrain-one brain hemisphere

servereCNS and limb defects

18

replace ZPA with latex bead covered in Hh

Hh protein coated beat micmickes effect of ZPA

19

how does hh control digit pattern

graded inhibition of glib proteolysis

shh is required to inhibit formation of gli3rep
-no shh gli3 rep on
-yes shh gli3 act on

binary-either gli3 rep on or gli3 act on

gli3rep formation is controlled by graded SHH

20

what does GLIact do for formation

nothing for digit formation-all about where gliREP is not

21

what does reduction of glib rep result in

dorsal CNS hypertrohpy

22

Shh relationship to GliACT and how affects phenotype of CNS

what does gliact induce

basically gli ACT and is not required-just can't have GliREP

pituity, hypo, sinal chord, etc.-need shh/gliact-having nothing would result in these not forming

23

what does

ss-/-

shh-/-, gli+/-

gli -/-

shh-/-m gli3 -/-

look like

ss-no brain differentiation/no finger differentiation-brain is almost deleted

shh/gli-dorsal part of brain is overgrown (hand gets messed up

gli-similar to adding another zpa-too much cns creation/too many digits

double knocout-dorsal cns hypertrohic/too many fingers

24

what happens between difference of reduced shh and enhanced in regards to dentate gyrus

reduced-depletetion of dentate gyrus

increase-increased dentate gyrus granule cells

25

encepholoy

product of pover production of CNS progenitor cells-link between Hh and stem cell proliferation

26

holoprosencephaly

dev disorder mainly characterized by incomplete midline formation during forebrain dev

-cyclopedia, single forebrain besiicle, single front tooth

results from shh defecinency (even haplo is enough)
-only in brain face tissues-other tissues are less sensivive?

27

smoothened and hpe

smoothened is critical drug/toxicologal target

not targeted by shh-targeted downstream

other ligands can turn smo on-neuro defects

28

what is required for production and secretion of mature shh+ how+what loss of function cholesterol

cholesterol!

Hh is usually large precurosor that is cleaved when added to cholesterol

results in HPE-probably due to lack of dhcr7 gene

29

Hh disease facts due to increased signalling

possibly result from mutation in negative transduction pathway (keep shh off)

dereased Gli3 repressor actiity (increased Shh/Gli3 act)

Many forms of cancer

Smo inhibitors may have benefits (so shh doesn't keep firing)

30

gli 3 diseases +congeniality

all are congenital

mutations lead to loss of gli3rep-three auto dominant dryness

overlord of digits, limb/brain defects

31

gliblastoma

due to increase of hh signaling

agresseive cns tumor

32

Medullablastoma

in cerebellum during dev

most common malignant tumor

occurs due to too much hh signaling
-or one ptc allele missing
-ptc inhibits pathway when shh not bound

anything resulting in too much shh pathway results in this

33

wnt/wingless

where are two intracellular pools of beta catenin

segment polarity gene in flies

cytoplasmic-invovled in signalling-regs target gene expression

cell membrane-involve din cell adhsion/tissue homeostasis-assocaited with caderhines an dadherins junctions

34

wnt pathway w/ wnt

wnt ligand binds to frz(frizzeeld) and arrow correctors

destruction complex dissocated-interrupts beta catenin phosphorylation

un phosphorylated beta catenin enters nucelus where finds to tcf/lef protein to turn on target gene expression

35

want pathway w/o b-catenin

tcf/lef proteins associate with groucho/grg to block target gene expression

tcf/lef proteins are bi-functional trx factors

36

destruction complex + what happens after

axin, APC, Gsk3 phosphorylate beta cattiness when no wnt

beta-catenin-P is substrate for beta TrCP degredation

37

PP2a

-PP2A removes P form beta catenin

38

wnt + cancer

simlpy changing beta catinin stability can cause cancer
-can result in constitutive activation-cancer

39

APC and cancer

linked with collateral cancer-too much beta catenin

40

what is canonical wnt pathway

regulation of beta cat into the nucleus

41

what is noncanonical wnt pathway

no beta cattiness or things that effect beta catenin

has tissue polarity function