Integrin Signaling in Oligodendrocytes and Its Importance in CNS Myelination

Figure 2

Integrins interact with other receptor types to mediate oligodendrocyte survival and proliferation. (a) Cooperative signaling between ErbB and integrin receptors. Binding of NRG to oligodendrocyte ErbB receptors normally evokes a proliferative response dependant on PI3K signaling. Upon α6β1-integrin ligation with LN2, NRG binding no longer induces PI3K activation, but rather initiates the MAPK survival response via Fyn signaling. (b) Joint regulatory control of survival in response to cooperative contactin and integrin receptor signaling. LN2 ligation of α6β1-integrin causes the dephosphorylation of Fyn’s negative regulatory site Tyr531. L1 binding to the contactin receptor induces the phosphorylation of Tyr420 (activation site) and Tyr531. Integration of extracellular cues via contactin/integrin crosstalk facilitates the dynamic control of Fyn to execute cellular functions affecting survival. (c) PDGFR-a and α6β1-integrin interact in oligodendrocyte lipid rafts. PI3K and Akt are activated upon concurrent ligation of PDGFR-α and α6β1-integrin with PDGF and LN2, respectively, to promote proliferation/survival.