Abstract
Long-term potentiation (LTP) and long-term depression (LTD) are important cellular mechanisms underlying learning and memory processes. N-Methyl-d-aspartate receptor (NMDAR)-dependent LTP and LTD play especially crucial roles in these functions, and their expression depends on changes in the number and single channel conductance of the major ionotropic glutamate receptor α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) located on the postsynaptic membrane. Structural changes in dendritic spines comprise the morphological platform and support for molecular changes in the execution of synaptic plasticity and memory storage. At the molecular level, spine morphology is directly determined by actin cytoskeleton organization within the spine and indirectly stabilized and consolidated by scaffold proteins at the spine head. Palmitoylation, as a uniquely reversible lipid modification with the ability to regulate protein membrane localization and trafficking, plays significant roles in the structural and functional regulation of LTP and LTD. Altered structural plasticity of dendritic spines is also considered a hallmark of neurodevelopmental disorders, while genetic evidence strongly links abnormal brain function to impaired palmitoylation. Numerous studies have indicated that palmitoylation contributes to morphological spine modifications. In this review, we have gathered data showing that the regulatory proteins that modulate the actin network and scaffold proteins related to AMPAR-mediated neurotransmission also undergo palmitoylation and play roles in modifying spine architecture during structural plasticity.
Highlights
Structural long‐term synaptic plasticity Long-term potentiation (LTP) and long-term depression (LTD) are two forms of synaptic plasticity orchestrated by glutamatergic signaling that have been extensively studied and are considered to be cellular correlates of learning and memory processes [1,2,3]
Depalmitoylation of Cell division cycle protein 42 (Cdc42) reverses this inhibition and increases the interaction between Cdc42 and RhoGDI and, in consequence, reduces a fraction of guanosine triphosphate (GTP)-bound Cdc42 and blocks Cdc42 targeting to the membrane. These results suggest dynamic palmitoylation/depalmitoylation cycling of Cdc42 that can be rapidly regulated by synaptic activity, most likely through an amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) activity feedback loop
The effector of Rac1, a phosphorylated P21-activated kinase (PAK), is locally activated and accumulated at synapses and colocalizes with postsynaptic density (PSD)-95 in cultured rat hippocampal neurons [196], and synaptic AMPAR is associated with activation of the Rac1/PAK/ LIMK1 pathway that is necessary for actin-mediated spine enlargement during LTP [203]
Summary
Structural long‐term synaptic plasticity Long-term potentiation (LTP) and long-term depression (LTD) are two forms of synaptic plasticity orchestrated by glutamatergic signaling that have been extensively studied and are considered to be cellular correlates of learning and memory processes [1,2,3]. In this review, we have gathered data to show the contribution and roles of palmitoylation of signaling proteins in the regulation of dendritic spine structural synaptic plasticity.
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