Role of Palmitoylation of Postsynaptic Proteins in Promoting Synaptic Plasticity

Matt, Lucas; Kim, Karam; Chowdhury, Dhrubajyoti; Hell, Johannes

doi:10.3389/fnmol.2019.00008

Cited by 79 publications

(79 citation statements)

References 176 publications

(326 reference statements)

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“…PATs, a family of enzymes consisting of 23 members in mammals, are referred to as “ZDHHCs” according to current nomenclature (see recent review [ 80 ]). They contain a highly conserved DHHC motif (Asp-His-His-Cys) within a Cys-rich domain which serves as the enzyme that adds the palmitate to protein substrate.…”

Section: Palmitoylation-depalmitoylation Dynamicsmentioning

confidence: 99%

“…Palmitoylation of AMPARs has been demonstrated to functionally regulate its trafficking between the plasma membrane and intracellular compartments under basal conditions and during synaptic plasticity in a palmitoylation site- and subunit-dependent manner ([ 86 , 252 ], recently reviewed in [ 80 , 81 ]). Current data also implies that palmitoylation of AMPARs is involved in the regulation of structural plasticity.…”

Section: Palmitoylation Of Ampar and Its Associated Scaffold Proteinsmentioning

confidence: 99%

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Roles of palmitoylation in structural long-term synaptic plasticity

Skup

2021

Mol Brain

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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.

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Section: Palmitoylation-depalmitoylation Dynamicsmentioning

confidence: 99%

Section: Palmitoylation Of Ampar and Its Associated Scaffold Proteinsmentioning

confidence: 99%

Roles of palmitoylation in structural long-term synaptic plasticity

Skup

2021

Mol Brain

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“…Although the palmitoylated cysteines share some common characteristics, there is no consensus palmitoylation sequence (Salaun et al, 2010). It is speculated that the proteinprotein interaction domain of DHHCs (e.g., ankyrin repeats in DHHC13/17, Src-homology 3 domain in DHHC6) plays critical roles in recognizing specific substrates (Fredericks et al, 2014;Verardi et al, 2017;Matt et al, 2019).…”

Section: Palmitoyl Acyltransferasesmentioning

confidence: 99%

Protein Palmitoylation in Leukocyte Signaling and Function

Yang

Chatterjee

et al. 2020

Front. Cell Dev. Biol.

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Palmitoylation is a post-translational modification (PTM) based on thioester-linkage between palmitic acid and the cysteine residue of a protein. This covalent attachment of palmitate is reversibly and dynamically regulated by two opposing sets of enzymes: palmitoyl acyltransferases containing a zinc finger aspartate-histidine-histidine-cysteine motif (PAT-DHHCs) and thioesterases. The reversible nature of palmitoylation enables fine-tuned regulation of protein conformation, stability, and ability to interact with other proteins. More importantly, the proper function of many surface receptors and signaling proteins requires palmitoylation-meditated partitioning into lipid rafts. A growing number of leukocyte proteins have been reported to undergo palmitoylation, including cytokine/chemokine receptors, adhesion molecules, pattern recognition receptors, scavenger receptors, T cell co-receptors, transmembrane adaptor proteins, and signaling effectors including the Src family of protein kinases. This review provides the latest findings of palmitoylated proteins in leukocytes and focuses on the functional impact of palmitoylation in leukocyte function related to adhesion, transmigration, chemotaxis, phagocytosis, pathogen recognition, signaling activation, cytotoxicity, and cytokine production.

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“…Of these, modification of GABA A Rs (Comenencia-Ortiz et al, 2014; Petrini and Barberis, 2014) and gephyrin (Tyagarajan and Fritschy, 2014; Zacchi et al, 2014; Kasaragod and Schindelin, 2018) are best described. Palmitoylation of both GABA A Rs and gephyrin result in enhanced surface localization (Matt et al, 2019), conversely ubiquitination (Luscher et al, 2011) or SUMOylation (Ghosh et al, 2016) of these proteins results in decreased synaptic accumulation. While phosphorylation of GABA A Rs controls both surface trafficking and removal (Comenencia-Ortiz et al, 2014), it also influences receptor diffusion in and out of synapses via gephyrin-dependent (Mukherjee et al, 2011) or independent mechanisms (Lévi et al, 2015).…”

Section: Multiple Signal Transduction Pathways Modulate Receptor-scafmentioning

confidence: 99%

Cellular Mechanisms Contributing to the Functional Heterogeneity of GABAergic Synapses

Campbell

Tyagarajan

2019

Front. Mol. Neurosci.

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GABAergic inhibitory neurotransmission contributes to diverse aspects of brain development and adult plasticity, including the expression of complex cognitive processes. This is afforded for in part by the dynamic adaptations occurring at inhibitory synapses, which show great heterogeneity both in terms of upstream signaling and downstream effector mechanisms. Single-particle tracking and live imaging have revealed that complex receptor-scaffold interactions critically determine adaptations at GABAergic synapses. Super-resolution imaging studies have shown that protein interactions at synaptic sites contribute to nano-scale scaffold re-arrangements through post-translational modifications (PTMs), facilitating receptor and scaffold recruitment to synaptic sites. Additionally, plasticity mechanisms may be affected by the protein composition at individual synapses and the type of pre-synaptic input. This mini-review article examines recent discoveries of plasticity mechanisms that are operational within GABAergic synapses and discusses their contribution towards functional heterogeneity in inhibitory neurotransmission.

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Role of Palmitoylation of Postsynaptic Proteins in Promoting Synaptic Plasticity

Cited by 79 publications

References 176 publications

Roles of palmitoylation in structural long-term synaptic plasticity

Roles of palmitoylation in structural long-term synaptic plasticity

Protein Palmitoylation in Leukocyte Signaling and Function

Cellular Mechanisms Contributing to the Functional Heterogeneity of GABAergic Synapses

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