Cell-Cell contacting and signalling Flashcards
complexes
forms at cell surface for interaction site and signalling centre
specialised contact
example of complexes
anchoring, tight and gap junction
anchoring junction
adherence junction and desmosome
induced by cadherins
tight junction
include claudins together and occludins on membrane
gap junction
intimate fusion by connexins
notch-delta
don’t occur at any specific complex
non-specialised such as selectins as well
organisation of junctions - starting from bottom
- communication junction
- anchoring junction
- occluding junction
- communicating junction
gap- allows communication between cells
primary importance
in plants - Plasmodesmata
- anchoring
stabilise epithelial sheet and cell next to each other
act as linkage
adherence - actin attachment site
desmosomes - intermediate filament attachment site
- occluding
tight(vertebrate) and septate(invertebrate) junctions
occlude movement of fluid and anything in fluid
act as block
heterophilic
different protein from signalling and target
1
communicating junction
1 - functional syncytia
membrane intact with small canals which allow small molecules in and out
1- full syncytia
some membrane break down completely
1- pores in membrane
align to next membrane
regulated by electro-chemical coupling of cells
common in excitable cells
1- example of excitable cells
cardiac muscles cells
1- junctions characteristic
very strong as ions can transfer from gap junction when excited
1- how gap junctions are formed
- 6 connexins get together to form pore likes structure
- with another 6 connexins = 2 connexons
- has charge in opening - limiting size of molecules and ions able to pass through 2nm apart
1- types of connexins
14 different types = mix and match
form connexons - heteromeric or homomeric
1- different gap junction formation
some sit individually
some brought together to form large structure = gap junction complex
very cell type dependent
1- example of gap junction regulation - light
Retina - high [Ca2+] channels close - stimulated by light
+ dopamine or mimics dark - gap junctions open
- dopamine of mimics bright light - closes
1- apoptosis
intracellular levels of [Ca2+] increases = junction closes
stops spreading of signals of cell death to other cells
1- example of gap junction complex
intercalated disc of heart
3
tight junction
3- function
very close - fluid cannot pass seal but through transmembrane protein
produces impermeable bonds between cells - limits paracellular permeability
3- limiting paracellular permeability
maintain osmotic variance across epithelial
e.g in gut or kidney
3- structure
claudin and occludin form bands at apes of epithelial
act as signalling centre
3- signalling centre of junction
pKa - regulate signalling cascade and G coupling protein
at membrane concentrates at tight junctions
ZONAB - change in junction like damage - released and migrates to nucleus and act as transcription fact
regulation gene expression
3- polarised membrane
different molecules in different areas of membrane
not about charge
3- example of polarised membrane
apical - upper
basolateral - lower
3- failure of tight junction
AI diseases
chronic inflammation
IBD
therefore important in innate immunity - oedema, diarrhoea and blood borne metastasis
3- cluster signalling molecules
claudin–claudin
occludin–occludin
2
anchoring junction
2- two forms
adherence junction
desmosomes
2- adherence junction
actin cytoskeleton - indirectly interacting with actins on neighbouring cells
2- desmosomes
intermediate filaments such as keratin - interact indirectly as well
2- cadherin
linking both forms and molecules between cell membrane
Ca2+ dependent adherence junction
2- cadherin structure
most have 5 cadherin-repeats and has Ca2+ binding sites between them
have intracellular domain when adding Ca2+ causing CC in extracellular region
2- increase in Ca2+
dimer comes together = rigid and open binding region therefore interact with neighbouring cadherin - around 1mM Ca2+
2- classical cadherin
E, N, P, Ve cadherin
adherence junction
2- Atypical cadherin
in desmosomes - desmoglein, desmocollin
2- example for junction - embryo
remove Ca2+ - lose adherence = lose tight junction therefore cell becomes loose
tight occurs if adherence occur
2- in classical
F-actin comes in on adapter protein + cadherin (exterior) = adherence junction = circumferential belt
2- in non-classical
keratin come in on adaptor + cadherin (exterior)
2- anchoring junction function
act as signalling centres - kinase and substrate
e.g. PI3 kinase
2- Wnt pathway
reservoir of signalling molecules - alpha/beta- catenin
regulate cell division
when active - alpha/beta catenin released into cell nucleus = signal and drive cell division
2- role - cell sorting 1
separating neuronal and epithelial - in vivo - in presence of N/E cadherin
centre express N-cadherin and rest on N and C terminus is E-cadherin
2 - role - cell sorting 2 - N and E-cadherin
N-cadherin remain together - starts invaginating and fuse = epithelial tube of N-cadherin expressing cells
E-cadherin on outer surface - separated
= CNS - N-cadherin tube
= skin - E-cadherin tube
2- failure to close tube
spina bifida - encephaloceles, hydranencephaly, iniencephaly
in the brain - anencephaly - no brain formation
non-specialised cells
Notch and delta
Selectins
regulatory steps of notch and delta
cell 1 -
notch ligand expresser - has the delta ligand
regulatory steps of notch and delta
cell 2 -
notch receptor - larger area on outer surface of Golgi lumen
regulatory steps of notch and delta 1
notch receptor was cleaved by protease
notch remains to other part by non-covalent interaction at cell membrane and meets delta ligand
regulatory steps of notch and delta 2 meeting delta ligand
signal passed causing CC therefore notch cleaved from cells 2 by TACE
causing CC and another enzyme (y-secretase) at intercellular part of receptor - released and carried to nucleus
CC
conformational change
TACE
extracellular membrane bound enzyme
cell 1 function
stop proliferation at receptor in basal cell
regulatory steps of notch and delta 3 - in nucleus
binds to transcription machinery
receptor tail - bind to protein - converts it from repressor to activator transcription
notch pathway
regulating gene expression - turned on
turning off notch pathway
cells carry on differentiating and cells divides - (-/-)
hyperproliferation and tumour form
notch expression at skin epidermis
1 - dividing cells - differentiates but not divide
2- differentiating - notch and receptor - induce and respond signalling - inhibit cell division and induce cell differentiation
3 - differentiated - no expression
Selectins
lectins - sugar binding proteins
what produces selectins
by veil endothelial cell during inflammation by cytokines
placed on the surface of cell membrane
selectin function
bind to ligand on WBC - slows them down and migrate out of tissue
activating E and P expressed - 1 bind platelets which degranulates and E - carbohydrate on glycoprotein of WBC = rolling
P-selectin glycoprotein ligand 1
mucin type glycoprotein in all WBC
E selectin
activated endothelial
P selectin
activated endothelial and platelets
often in veins not arteries
basal cells
induced signal but not respond
also has melanocytes
regulatory of notch and delta in Golgi
cleave off ad transport to plasma membrane
