Figure 8: Gpr56 promotes OPC proliferation through inhibiting differentiation.
From: The adhesion GPCR Gpr56 regulates oligodendrocyte development via interactions with Gα12/13 and RhoA
Model of Gpr56 function in OPCs. In WT OPCs, Gpr56 couples to Gα12/13 and activates RhoA, which prevents terminal differentiation and indirectly promotes OPC proliferation (dashed arrow) by maintaining the OPC in an immature, proliferative state. OPC proliferation is directly regulated via interactions between neuron-secreted PDGF-A and OPC-bound PDGFRα. In Gpr56 (stl13/stl13) mutant OPCs, impaired autoproteolytic cleavage reduces Gpr56 signalling capacity, leading to loss of RhoA activation. Reduced RhoA signalling alleviates RhoA inhibition on terminal differentiation (green arrow), which indirectly causes a decrease in OPC proliferation (red dashed lines) as OPCs differentiate at the expense of proliferation.
