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. 2018 Jul 31;12:221. doi: 10.3389/fncel.2018.00221

FIGURE 5.

FIGURE 5

Model of known signaling pathways and interactions downstream of DCC in netrin-1 dependent axon guidance. DCC interacts with several enzymes and adaptor proteins and components of the actin and microtubule cytoskeletons in the absence of netrin-1, forming a “primed” signaling complex, which can rapidly initiate responses to ligand binding. Netrin-1 increases valency through multimerization of DCC homodimers. This clustering brings intracellular domains of the receptors into close apposition, forming a scaffold for the recruitment and activation of several proteins. Solid green arrows denote direct steps in activation, whereas dashed green arrows are known connections that may have intermediates. These pathways together modify the intracellular environment to promote directional axon outgrowth in response to netrin-1. AKAP79, A kinase anchoring protein 79; ARP2/3, actin-related protein 2/3 complex; CDC42, cell division control protein 42; DCC, deleted in colorectal cancer; DOCK1, dedicator of cytokinesis 1; ELK1, ETS transcription factor; ERK, mitogen activated protein kinase; ERM, ezrin-radixin-moesin; FAK, focal adhesion kinase; FN3, fibronectin type 3 domain; Ig, immunoglobulin domain; JNK1, c-Jun N-terminal kinase 1; MARCKS, myristoylated alanine-rich C kinase substrate; MEK, mitogen activated protein kinase kinase; MENA, mammalian enabled; MYOII, myosin II; MYOX, unconventional myosin X; NCK1, NCK adaptor protein 1; N-WASP, neuronal Wiskott–Aldrich syndrome protein; PAK1, protein associated kinase 1; PKA, protein kinase A; PKB, protein kinase B; PKC, protein kinase C; PLCγ, phospholipase C gamma; RAC1, Ras-related C3 botulinum toxin substrate 1; RHOA, Ras homolog gene family member A; ROCK, Rho associated protein kinase; SFKs, Src family kinases; SNAP25, synaptosomal associated protein 25; SYTX1, syntaxin-1; TIAM1, T-lymphoma invasion and metastasis protein 1; TRIM9, tripartite motif protein 9; TRIO, triple domain functional protein; VAMP2, vesicle associated membrane protein 2; VAMP7, vesicle associated membrane protein 7; VASP, vasodilator stimulated phosphoprotein.