Figure 7.

Proposed functions of PIKE-L during LTP formation. PIKE-L complexes with GRIP1 under basal condition at the excitatory synapses. During NMDAR-dependent LTP (e.g. TBS or glycine stimulation), the activation of NMDAR triggers the GluA2-associated PI3K activation. The newly formed PIP₃ serves as a signal for the tethering of PIKE-L/GRIP1 complex to the GluA2 of the intracellular pool, where PIKE-L sustains the activity of GluA2-associated PI3K. The PIKE-L/GRIP1/GluA2 complex will then be transported to the synaptic surface, where the GRIP1 promotes the anchorage of GluA2 on the cell surface to facilitate the formation of LTP.