Fig. 5

Roles of palmitoylation during structural LTP. During LTP, more AMPARs are recruited to the postsynaptic membrane via exocytosis and anchored on an enlarged PSD and on Ankyrin-G, which more densely populate the submembrane region than in the basal state. Ankyrin-G molecules are targeted to perisynaptic sites of the spine head and spine neck to stabilize the spine structure through palmitoylation and binding to spectrin (1:1), which is a cytoskeletal protein that lines the intracellular side of the plasma membrane interacting with actin cytoskeletal protein. AMPAR, 4.1 N, spectrin, actin and associated molecules form a membrane-associated periodic skeleton (MPS) structure observed in spines, but the extent to which it exists and how it develops in dendrites remain unclear [340, 341]. Palmitoylation targets Rac1, Cdc42, Ras and LIMK1 to spine membrane where Rac1 and Cdc42 activate PAK. Next, phosphorylated LIMK1 by activated PAK phosphorylates Cofilin and inhibits its depolymerizing activity. Palmitoylated Ras seems to participate in spine morphological modification through downstream MEK/ERK signaling pathway. In addition, through downstream WAVE and WASP, Rac1 and Cdc42 also regulate Arp2/3-mediated actin polymerization, which can be inhibited by PICK1. Palmitoylation also seems to facilitate assembly of the complex containing AMPAR, ABP-L, N-cadherin and δ-catenin on the postsynaptic membrane, linking AMPAR trafficking to the actin cytoskeleton network through Rho signaling. Regulation of functional and structural plasticity is a highly sophisticated process which needs precise timing of coordinated work of plenty of factors. Interplay between the processes described above and other, unknown factors, may lead to enhanced synaptic transmission and enlarged spines. The sketch was prepared based on the data collected in this review. One squiggle denotes one or more palmitoyl chains attached to the target protein; Spectrin line icon denotes several spectrin molecules