Complement system in neuronal development and plasticity (Homo sapiens)
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Description
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.
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