Complement system in neuronal development and plasticity (WP5090)

Homo sapiens

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The complement system can be activated through the classical, alternative or leptin pathway. Antigen-antibody complexes are recognised by C1q, which causes the sequential cleavages of C1r and C1s (classical pathway). Collectins and ficolins bind to MBL-associated serine proteases (lectin pathway). Activation of the alternative pathway involves spontaneous hydrolysis of C3 and subsequent cleavages by factors B, D and I. All cascades converge into a common pathway producing opsonins (C3b) that target cells for phagocytosis. Upon increasing activation, subcomponents C5b-C9 form the membrane attack complex (MAC), which induces cellular lysis. Smaller anaphylatoxins (C3a, C4a and C5a) mediate chemotaxis of immune cells and vasoactivation. Furthermore, complement regulator proteins such as SERPING1, Factor H, CSMD1 and CD59 negatively regulate the cascade. Additionally, C3d/CR2 signaling inhibits adult NPC proliferation (green). Anaphylatoxins and lectin components enhance migration (green). C5a-C5aR1 signaling contributes to NPC polarity and proliferation (blue). Apoptotic signaling, TGFβ, C1q, C3b and CR3 mediate selective synaptic pruning of weak synapses.

Authors

Lisa Koole , Egon Willighagen , and Eric Weitz

Activity

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Organisms

Homo sapiens

Communities

Annotations

Cell Type Ontology

astrocyte neural progenitor cell microglial cell neuron

Pathway Ontology

complement system pathway neurodevelopmental disorder pathway signaling pathway pertinent to the brain and nervous system

Participants
Query Drugst.One

Label Type Compact URI Comment
Ca2+ Metabolite chebi:29108
H2O Metabolite chebi:15377
Pi Metabolite chebi:24838
Mg2+ Metabolite chebi:18420
ATP Metabolite chebi:30616
ADP Metabolite chebi:456216
Phosphatidylserine Metabolite chebi:18303
Phosphoethanolamine Metabolite chebi:17553
HTRA2 GeneProduct ncbigene:27429
BAK1 GeneProduct ncbigene:578
PRKCI GeneProduct ncbigene:5584
MARK3 GeneProduct ncbigene:4140
XIAP GeneProduct ncbigene:331
PARD6B GeneProduct ncbigene:84612
PRKCZ GeneProduct ncbigene:5590
C5AR2 GeneProduct ncbigene:27202
GAS6 GeneProduct ncbigene:2621
SCRIB GeneProduct ncbigene:23513
MERTK GeneProduct ncbigene:10461
FASLG GeneProduct ncbigene:356
CRB2 GeneProduct ncbigene:286204
MFGE8 GeneProduct ncbigene:4240
CX3CR1 GeneProduct ncbigene:1524
LLGL2 GeneProduct ncbigene:3993
ITGB3 GeneProduct ncbigene:3690
MARK2 GeneProduct ncbigene:2011
CRB1 GeneProduct ncbigene:23418
PARD6A GeneProduct ncbigene:50855
DIABLO GeneProduct ncbigene:56616
PROS1 GeneProduct ncbigene:5627
PATJ GeneProduct ncbigene:10207
DLGAP5 GeneProduct ncbigene:9787
DEDD GeneProduct ncbigene:9191
FAS GeneProduct ncbigene:355
MARK1 GeneProduct ncbigene:4139
CASP7 GeneProduct ncbigene:840
AXL GeneProduct ncbigene:558
ITGAV GeneProduct ncbigene:3685
CYCS GeneProduct ncbigene:54205
PARD6G GeneProduct ncbigene:84552
CASP9 GeneProduct ncbigene:842
TYRO3 GeneProduct ncbigene:7301
BAX GeneProduct ncbigene:581
MPP5 GeneProduct ncbigene:64398
PARD3 GeneProduct ncbigene:56288
BID GeneProduct ncbigene:637
IFNG GeneProduct ncbigene:3458
CASP8 GeneProduct ncbigene:841
CAP1 GeneProduct ncbigene:10487
CASP10 GeneProduct ncbigene:843
APAF1 GeneProduct ncbigene:317
CX3CL1 GeneProduct ncbigene:6376
C6 GeneProduct ncbigene:729
ATP8B2 GeneProduct ncbigene:57198
CR1 GeneProduct ncbigene:1378
CD55 GeneProduct ncbigene:1604 DAF
TGFB3 GeneProduct ncbigene:7043
MBP GeneProduct ncbigene:4155
CR2 GeneProduct ncbigene:1380
ITGB2 GeneProduct ncbigene:3689
FCN3 GeneProduct ncbigene:8547
CD46 GeneProduct ncbigene:4179 Membrane Cofactor Protein
C1R GeneProduct ncbigene:715
C4BPB GeneProduct ncbigene:725
CFP GeneProduct ncbigene:5199
COLEC10 GeneProduct ncbigene:10584
C4BPA GeneProduct ncbigene:722
COLEC12 GeneProduct ncbigene:81035
C5 GeneProduct ncbigene:727
C8A GeneProduct ncbigene:731
C3 GeneProduct ncbigene:718
PLSCR1 GeneProduct ncbigene:5359
C7 GeneProduct ncbigene:730
VTN GeneProduct ncbigene:7448
CFD GeneProduct ncbigene:1675
TGFB2 GeneProduct ncbigene:7042
PLSCR4 GeneProduct ncbigene:57088
SERPING1 GeneProduct ncbigene:710
TGFB1 GeneProduct ncbigene:7040
MBL1P GeneProduct ncbigene:8512
C8G GeneProduct ncbigene:733
ATP11C GeneProduct ncbigene:286410
CFBb GeneProduct ncbigene:629
C5AR1 GeneProduct ncbigene:728
CFH GeneProduct ncbigene:3075
CFB GeneProduct ncbigene:629
MBL2 GeneProduct ncbigene:4153
FCN1 GeneProduct ncbigene:2219
C2 GeneProduct ncbigene:717
MASP2 GeneProduct ncbigene:10747
ITGAM GeneProduct ncbigene:3684
CSMD1 GeneProduct ncbigene:64478
ITGAX GeneProduct ncbigene:3687
C4B GeneProduct ncbigene:721
C1QB GeneProduct ncbigene:713
FCN2 GeneProduct ncbigene:2220
ATP11A GeneProduct ncbigene:23250
COLEC11 GeneProduct ncbigene:78989
C1QA GeneProduct ncbigene:712
C3AR1 GeneProduct ncbigene:719
ATP10A GeneProduct ncbigene:57194
C8B GeneProduct ncbigene:732
ATP8B3 GeneProduct ncbigene:148229
C1QC GeneProduct ncbigene:714
C4A GeneProduct ncbigene:720
C1S GeneProduct ncbigene:716
SUSD4 GeneProduct ncbigene:55061
CASP3 GeneProduct ncbigene:836
CFI GeneProduct ncbigene:3426
CLU GeneProduct ncbigene:1191
C9 GeneProduct ncbigene:735
ATP8B1 GeneProduct ncbigene:5205
PLSCR3 GeneProduct ncbigene:57048
MASP1 GeneProduct ncbigene:5648
CFBa GeneProduct ncbigene:629
CD59 GeneProduct ncbigene:966
tBID GeneProduct ncbigene:637 Truncated BID
C2a Protein reactome:R-HSA-166780
C2b Protein reactome:R-HSA-166781
C3a Protein reactome:R-HSA-166828
C3b Protein reactome:R-HSA-166832
C5a Protein reactome:R-HSA-173677
C3dg Protein reactome:R-HSA-3266505
C3f Protein reactome:R-HSA-976779

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