Cel-Cel communicatie
H1 BASISCONCEPTEN............................................................................................................................................................... 3
1) EVOLUTIE/ BASISCONCEPTEN............................................................................................................................................................ 3
1.1 Quorum sensing......................................................................................................................................................................3
1.2 Directe cel-cel communicatie..................................................................................................................................................3
1.3 Indirecte communicatie..........................................................................................................................................................3
2) CEL-CEL COMMUNICATIE: KORTE EN LANGE AFSTANDSRELATIES...............................................................................................................3
3) BINDINGS- EN EFFECTORSPECIFICITEIT.................................................................................................................................................4
3.1 Bindingsspecificiteit................................................................................................................................................................4
3.2 Effectorspecificiteit.................................................................................................................................................................4
3.3 Pleiotropie...............................................................................................................................................................................4
3.4 Redundantie...........................................................................................................................................................................4
4) ALGEMENE EIGENSCHAPPEN LIGAND – RECEPTOR SYSTEEM.....................................................................................................................5
4.1 Categorieën............................................................................................................................................................................5
4.2 Classificatie van membraangebonden receptoren.................................................................................................................5
4.3 Bindingsaffiniteit....................................................................................................................................................................6
5) ALGEMENE EIGENSCHAPPEN SIGNAALTRANSDUCTOREN..........................................................................................................................8
5.1 Eiwitkinasen............................................................................................................................................................................8
5.2 GTP-bindende eiwitten...........................................................................................................................................................8
5.3 Adaptoreiwitten......................................................................................................................................................................8
5.4 Skeleteiwitten = scaffold proteïnen........................................................................................................................................9
5.5 Secundaire boodschappers.....................................................................................................................................................9
6) REGULATIEMECHANISMEN................................................................................................................................................................9
6.1 Regulatie thv ligand................................................................................................................................................................9
6.2 Regulatie thv receptor............................................................................................................................................................9
H2 SPECIFIEKE SIGNAALSYSTEMEN........................................................................................................................................... 9
1) DIRECTE WERKING VAN NO............................................................................................................................................................. 9
1.1 Nitroglycerine.........................................................................................................................................................................9
1.2 eNOS.......................................................................................................................................................................................9
1.3 iNOS........................................................................................................................................................................................9
2) NUCLEAIRE RECEPTOREN................................................................................................................................................................10
2.1 Algemeen..............................................................................................................................................................................10
2.2 Structuur...............................................................................................................................................................................10
2.3 Experiment............................................................................................................................................................................10
3) G-EIWIT GEKOPPELDE RECEPTOREN..................................................................................................................................................10
3.1 Algemeen..............................................................................................................................................................................10
3.2 Cyclus G-eiwit.......................................................................................................................................................................11
3.3 Ga subeenheid......................................................................................................................................................................11
3.4 Adrenerg receptoren als model............................................................................................................................................11
3.5 B-adrenergische receptoren.................................................................................................................................................12
3.6 Kenmerken GPCR....................................................................................................................................................................1
3.7 B-AR ligand analogen als medicijn.........................................................................................................................................1
4) RECEPTOREN MET ENZYMATISCHE WERKING........................................................................................................................................1
4.1 RTKs algemeen.......................................................................................................................................................................1
4.2 Activatie RTKs.........................................................................................................................................................................2
4.3 Binding signaaleiwitten..........................................................................................................................................................2
4.4 RTKs samenvatting.................................................................................................................................................................3
5) CYTOKINERECEPTOREN.................................................................................................................................................................... 3
5.1 JAKs.........................................................................................................................................................................................3
5.2 Signalering via STAT factoren.................................................................................................................................................3
5.3 Cytokinereceptoren samenvatting.........................................................................................................................................4
6) INHIBITIE VAN SIGNALERING DOOR RTKS/ CYTOKINERECEPTOREN............................................................................................................4
7) TOLL-LIKE RECEPTOREN................................................................................................................................................................... 4
8) ROL VAN UBIQUITINE IN SIGNAALTRANSDUCTIE....................................................................................................................................4
8.1 Ubiquitinylatie in NF – kB signaalweg....................................................................................................................................5
,8.2 Ubiquitine als scaffold............................................................................................................................................................5
8.3 Samenvatting TLRs/ Ubiquitinatie..........................................................................................................................................5
, H1 Basisconcepten
1) Evolutie/ basisconcepten
1.1 Quorum sensing
Quorum = minimumaantal leden dat aanwezig moet zijn om in vergadering besluiten te nemen
Lage densiteit (planktonisch) => geen effect en binding
Hoge densiteit (symbiontisch) => wel binding en effect
Experiment met feromonen en luciferase
1.2 Directe cel-cel communicatie
Gap junctions: connexons en connexines
Kleine signaalmoleculen: Ca2+, cAMP, glucose, …
Snelle, synchrone reactie
1.3 Indirecte communicatie
Via extracellulaire signaalmoleculen
o Synthese en secretie ligand
o Transport ligand
o Binding tussen ligand en receptor
o Activatie/ synthese signaaltransductoren
o Activatie effectoreiwitten
o Korte/ lange termijneffecten
o Negatieve feedback en verwijderen ligand
2) Cel-cel communicatie: korte en lange afstandsrelaties
Endocriene cel-cel communicatie
o Hormonen (signaalmoleculen): worden aangemaakt in gespecialiseerde klieren
o Transport naar verafgelegen doelwitcellen via bloedbaan
Paracriene cel-cel communicatie
o Signalisatie beperkt tot cellen in onmiddellijke omgeving.
o Liganden binden op nabijgelegen cellen (bv cytokines)
o Synaptische communicatie waarbij neurotransmitters gesecreteerd worden in de
synaptische spleet. Dit is een zeer snelle en gerichte vorm van paracriene signalisering
Juxtacriene cel-cel communicatie
o Communicatie via plasmamembraan verankerde liganden
o Geen secretie van signaal
o Belangrijke rol bij onder andere hematopoëse
Autocriene cel-cel communicatie
o Liganden werken in op dezelfde cellen waardoor ze gesecreteerd werden (bv IL-2 bij
geactiveerde T-cellen)
o Aberrante autocriene signalisatie door groeifactoren komt vaak voor in kanker
H1 BASISCONCEPTEN............................................................................................................................................................... 3
1) EVOLUTIE/ BASISCONCEPTEN............................................................................................................................................................ 3
1.1 Quorum sensing......................................................................................................................................................................3
1.2 Directe cel-cel communicatie..................................................................................................................................................3
1.3 Indirecte communicatie..........................................................................................................................................................3
2) CEL-CEL COMMUNICATIE: KORTE EN LANGE AFSTANDSRELATIES...............................................................................................................3
3) BINDINGS- EN EFFECTORSPECIFICITEIT.................................................................................................................................................4
3.1 Bindingsspecificiteit................................................................................................................................................................4
3.2 Effectorspecificiteit.................................................................................................................................................................4
3.3 Pleiotropie...............................................................................................................................................................................4
3.4 Redundantie...........................................................................................................................................................................4
4) ALGEMENE EIGENSCHAPPEN LIGAND – RECEPTOR SYSTEEM.....................................................................................................................5
4.1 Categorieën............................................................................................................................................................................5
4.2 Classificatie van membraangebonden receptoren.................................................................................................................5
4.3 Bindingsaffiniteit....................................................................................................................................................................6
5) ALGEMENE EIGENSCHAPPEN SIGNAALTRANSDUCTOREN..........................................................................................................................8
5.1 Eiwitkinasen............................................................................................................................................................................8
5.2 GTP-bindende eiwitten...........................................................................................................................................................8
5.3 Adaptoreiwitten......................................................................................................................................................................8
5.4 Skeleteiwitten = scaffold proteïnen........................................................................................................................................9
5.5 Secundaire boodschappers.....................................................................................................................................................9
6) REGULATIEMECHANISMEN................................................................................................................................................................9
6.1 Regulatie thv ligand................................................................................................................................................................9
6.2 Regulatie thv receptor............................................................................................................................................................9
H2 SPECIFIEKE SIGNAALSYSTEMEN........................................................................................................................................... 9
1) DIRECTE WERKING VAN NO............................................................................................................................................................. 9
1.1 Nitroglycerine.........................................................................................................................................................................9
1.2 eNOS.......................................................................................................................................................................................9
1.3 iNOS........................................................................................................................................................................................9
2) NUCLEAIRE RECEPTOREN................................................................................................................................................................10
2.1 Algemeen..............................................................................................................................................................................10
2.2 Structuur...............................................................................................................................................................................10
2.3 Experiment............................................................................................................................................................................10
3) G-EIWIT GEKOPPELDE RECEPTOREN..................................................................................................................................................10
3.1 Algemeen..............................................................................................................................................................................10
3.2 Cyclus G-eiwit.......................................................................................................................................................................11
3.3 Ga subeenheid......................................................................................................................................................................11
3.4 Adrenerg receptoren als model............................................................................................................................................11
3.5 B-adrenergische receptoren.................................................................................................................................................12
3.6 Kenmerken GPCR....................................................................................................................................................................1
3.7 B-AR ligand analogen als medicijn.........................................................................................................................................1
4) RECEPTOREN MET ENZYMATISCHE WERKING........................................................................................................................................1
4.1 RTKs algemeen.......................................................................................................................................................................1
4.2 Activatie RTKs.........................................................................................................................................................................2
4.3 Binding signaaleiwitten..........................................................................................................................................................2
4.4 RTKs samenvatting.................................................................................................................................................................3
5) CYTOKINERECEPTOREN.................................................................................................................................................................... 3
5.1 JAKs.........................................................................................................................................................................................3
5.2 Signalering via STAT factoren.................................................................................................................................................3
5.3 Cytokinereceptoren samenvatting.........................................................................................................................................4
6) INHIBITIE VAN SIGNALERING DOOR RTKS/ CYTOKINERECEPTOREN............................................................................................................4
7) TOLL-LIKE RECEPTOREN................................................................................................................................................................... 4
8) ROL VAN UBIQUITINE IN SIGNAALTRANSDUCTIE....................................................................................................................................4
8.1 Ubiquitinylatie in NF – kB signaalweg....................................................................................................................................5
,8.2 Ubiquitine als scaffold............................................................................................................................................................5
8.3 Samenvatting TLRs/ Ubiquitinatie..........................................................................................................................................5
, H1 Basisconcepten
1) Evolutie/ basisconcepten
1.1 Quorum sensing
Quorum = minimumaantal leden dat aanwezig moet zijn om in vergadering besluiten te nemen
Lage densiteit (planktonisch) => geen effect en binding
Hoge densiteit (symbiontisch) => wel binding en effect
Experiment met feromonen en luciferase
1.2 Directe cel-cel communicatie
Gap junctions: connexons en connexines
Kleine signaalmoleculen: Ca2+, cAMP, glucose, …
Snelle, synchrone reactie
1.3 Indirecte communicatie
Via extracellulaire signaalmoleculen
o Synthese en secretie ligand
o Transport ligand
o Binding tussen ligand en receptor
o Activatie/ synthese signaaltransductoren
o Activatie effectoreiwitten
o Korte/ lange termijneffecten
o Negatieve feedback en verwijderen ligand
2) Cel-cel communicatie: korte en lange afstandsrelaties
Endocriene cel-cel communicatie
o Hormonen (signaalmoleculen): worden aangemaakt in gespecialiseerde klieren
o Transport naar verafgelegen doelwitcellen via bloedbaan
Paracriene cel-cel communicatie
o Signalisatie beperkt tot cellen in onmiddellijke omgeving.
o Liganden binden op nabijgelegen cellen (bv cytokines)
o Synaptische communicatie waarbij neurotransmitters gesecreteerd worden in de
synaptische spleet. Dit is een zeer snelle en gerichte vorm van paracriene signalisering
Juxtacriene cel-cel communicatie
o Communicatie via plasmamembraan verankerde liganden
o Geen secretie van signaal
o Belangrijke rol bij onder andere hematopoëse
Autocriene cel-cel communicatie
o Liganden werken in op dezelfde cellen waardoor ze gesecreteerd werden (bv IL-2 bij
geactiveerde T-cellen)
o Aberrante autocriene signalisatie door groeifactoren komt vaak voor in kanker
