Neurexin-Neuroligin Synaptic Complex Regulates Schizophrenia-Related DISC1/Kal-7/Rac1 “Signalosome”

Figure 7

Schematic illustration of possible consequences of the NR1:NL1 interaction with the DISC1/Kal-7/Rac1 signalosome. At the baseline condition, NL1 forms homodimer interacting with NMDA receptor while DISC1 binds Kal-7, blocking the access of Kal-7 to Rac1. Upon synaptic activity and activation of NMDA receptors, NX1β is cleaved from the presynaptic membrane leading to partial cleavage of NL1 from the postsynaptic membrane followed by the release of NL1 from NMDA receptor and DISC1 from Kal-7. After the shedding, NL1 is no longer a dimer which probably changes the mobility of N-terminally truncated NL1, and it can diffuse allowing NL1 to bind Kal-7 and in turn lead to the activation of Rac1. These events eventually allow NL1 to bind Kal-7 and in turn lead to the activation of Rac1. Additionally, binding of ecto-NX1β tο NL1 results in NR1 subunit phosphorylation at S896 and S897 and phosphorylation of ERK and Akt.