Fig. 3
From: Roles of palmitoylation in structural long-term synaptic plasticity
PSD-95 protein interactions are interrupted by Ca2+ influx which affects also PSD-95 relation with actin networks. A. PSD-95 is anchored on the postsynaptic membrane via palmitoylation at Cys3 and Cys5 and α-actinin anchoring. Through binding the N-terminus of palmitoylated PSD-95, CDKL5 is targeted to postsynaptic sites where it forms a complex with Rac1 to regulate the actin cytoskeleton via the Rac1 signaling pathway. B. Upon activity-induced Ca2+ influx through NMDAR, activated calmodulin (CaM), due to Ca2+ binding, caps the N-terminal of PSD-95, leading to blocked accessibility of palmitoylation sites and binding sites for CDKL5 and α-actinin. This process results in downregulation of PSD-95 palmitoylation and release of PSD-95 from the postsynaptic membrane. As a result, CDKL5 will also be released from the synapses and fail to form complexes with Rac1. Illustration based on [102, 274,275,276,277,278]. One squiggle denotes one palmitoyl chain attached to PSD-95