Figure 1.

Signaling pathways through Gas6-TAM implicated in Schwann myelination.

(A) Endogenous Gas6, which is secreted by neurons and endothelial cells binds to Tyro3. Since Tyro3 only expresses in Schwann cells, not in oligodendrocytes, as well as no-glial cells, Gas6 induced Tyro3 activation specifically regulates myelination in Schwann cells. Tyro3 downstream molecule Fyn tyrosine kinase is activated by the correlation between axons and Schwann cells. Activated Fyn regulates the expression levels of Oct6 and Krox6, acting through Akt signaling (a). Also, Fyn directly mediates phosphorylation of cytohesin-1, which promotes Arf6 activation (b). Finally, signal transduction in both pathways controls Schwann cell myelination. Gas6/TAM signal transduction participates in cell survival, cell proliferation, and actin rearrangement in oligodendrocytes as well as no-glial cells. (c). LINGO-1 inhibits the phosphorylation of Fyn and oligodendrocytes myelination. (B) Gas6/TAM signaling is well established as regulator of cell survival, cell proliferation, and actin dymanics in non-glial cells. Arf6: ADP-ribosylation factor 6; ERK1/2: extracellular signal-regulated kinase 1/2; Gas6: growth arrest-specific gene 6; Grb2: growth factor receptor-bound protein 2; LINGO-1: leucine rich repeat and immunoglobin-like domain-containing protein 1; NR-κB: nuclear factor kappaB; NRG1: neuregulin 1; Oct6: POU domain, class 3, transcription factor 1; PI3: phosphoinositide-3; PKC: protein kinase C; PLC: phospholipase C; SOS: son of sevenless; TAM: the TYRO3, AXL (also known as UFO) and MERTK; Tyro3: tyrosine-protein kinase receptor.