Figure 5

A glutamatergic synapse focusing on the organization of DLG4 protein. A) The increased NRG1-ERBB4 signaling may lead to hypophosphorylation of GRIN complex [16] or internalization of GRIN complex [30] in postsynaptic neuron. Less NMDA receptor will be available on the membrane and the capacity for cation influx (mainly calcium influx) will decrease. B) A direct interaction between CACNG2 and DLG4 mediates the synaptic delivery of GRIA complex [38]. The anchored CACNG2 may recruit the GRIA complex to the synaptic region [20] and increase the cation influx. Phosphorylation of DLG4 will release it from the cytoskeleton [32] and fail to recruit the GRIA complex efficiently. C) Taken together, DLG4 links two mechanisms to decrease the cation influx at the synaptic area. The presence of gene variations in both NRG1 and CACNG2 may thus create synergistic effect to affect the influx of Ca²⁺.