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samenvatting Cel IV: cel-cel communicatie
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samenvatting Cel IV: partim cel-cel communicatie (Gerlo)
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Cel-cel communicatieEvolutie
- Signaaloverdracht eencelligen sterk geconserveerd: ligand-receptor => signaaltransductie
- Bv. quorum sensing bij inktvis en bacteriën (feromonen)
Types cel-cel communicatie
Direct: gespecialiseerd
- Gap-junctions (=> connexons => connexines)
- Kleine signaalmoleculen: Ca2+, cAMP, glucose, vitamines
- Synchrone, snelle reactie
Indirect:
- Signaliserende cel => signaalmoleculen
- Receptoren op doelwitcel
- Type respons afh. v. signaaltransductoren
- Effect :
o Korte termijn : functie wijziging
o Lange termijn : genexpressie wijziging
Afstand
Endocrien :
- Veraf gelegen cellen
- Hormonen (aangemaakt in gespecialiseerde klieren)
- Transport via bloedbaan
Paracrien
- Nabijgelegen cellen
- Bv. Cytokines
- Synaptische communicatie : secretie neurotransmitters in synaptische spleet
o Snel + gericht
Autocrien
- Ligand en receptor op =e cel
- Groeifactoren !kanker
Direct = juxtacrien
- Membraanverankerde liganden
Specificiteit
Binding
- Liganden binden op specifieke receptoren (complementair)
- MAAR sommige liganden hebben meerdere receptoren en vice versa
Effector
- Respons van ligand/receptor binding is cel afh.
Pleiotropie
- =e ligand lokt versch. reacties uit op versch. celtypes en versch. receptoren
, Redundantie
- Versch. liganden en versch. receptoren lokken toch =e respons uit
Classificatie liganden
Lipofiel + intracellulaire receptoren
- Bv. steroïden, thyroxine, retinoïnezuur
Lipofiel + membraangebonden receptoren
- Bv. prostaglandines
Hydrofiel + membraangebonden receptoren
- Bv. neurotransmitters, (poly)peptide hormone
Classificatie receptoren
Membraan-verankerde
- Ion-kanaal:
o Ligand-binding => structurele wijziging in receptor => openen/sluiten
membraanporiën
o Doorgang specifieke ionen => wijziging membraanpotentiaal
o Neurotransmitters
o Zeer snel effect
- G-eiwit:
o Ligand-binding => structurele wijziging in receptor => activatie G-eiwit => enzymen
(in)activeren/ ionkanalen openen/sluiten
o Kleine liganden bv. adrenaline
- Enzym:
o Receptoren bevatten katalytische domein (intracellulair)/ binden enzymen
o Ligand-binding => receptorcomplex-vorming (dimerisatie) => activatie enzym
o Kinase (Tyr, Thr, Ser), fosfatase, guanylaat-cyclase, RNase
- Signaalplatformen:
o Receptoren vormen oligomere clusters => platform voor adoptoreiwitten: brug
tussen receptor en effectoreiw
Cytoplasmatische/nucleaire
Bindingsaffiniteit
- Reversibel: L + R <-> LR
- Associatieconstante KA: [LR]/[L][R]
- Dissociatieconstante KD: [L][R]/[LR] = 1/ KA= [L] waarbij 50% vd receptoren gebonden is
- Specifiek per ligand-receptor binding
- Fractionele receptorbezetting FR: [LR]/ [LR] + [LR]
o Reeds fysiologische respons bij lage FR
- Liganden w na secretie verdund => hoge affiniteit voor receptor
- Neurotransmitters in synaptische spleet (hoge conc.) => lage affiniteit voor receptor
- Cellen met Epo-R laten binden met Epo gelabeld met I 125 (toen. conc.): saturatie
bindingsstudie => totale binding, specifiek en niet-specifiek
- Scatchard plot: [LR]/[L]= KA. R0- KA.[LR]
o Rechte: : [LR]/[L] tov [LR]
o Rico = - KA
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