Regulation of enzymatic activity by active site fatty acylation. A new role for long chain fatty acid acylation of proteins.

Berthiaume, Luc G.; Deichaite, Ida; Peseckis, Steven M.; Resh, Marilyn D.

doi:10.1016/s0021-9258(17)37399-4

Cited by 69 publications

(15 citation statements)

References 35 publications

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“…Majority of brain metabolic energy is used on synaptic transmission and changes in synapse strength can alter energy expenditure (Harris, Jolivet, & Attwell, 2012). As mitochondrial enzymes have been shown to be inhibited by palmitoylation (Berthiaume, Deichaite, Peseckis, & Resh, 1994; Corvi, Soltys, & Berthiaume, 2001), the activity-induced reduction in metabolic protein palmitoylation observed in this study may serve a regulatory function to enhance enzymatic activity during neuronal stimulation and synaptic transmission.…”

Section: Resultsmentioning

confidence: 68%

Synaptic Activity-Dependent Changes in the Hippocampal Palmitoylome

Nasseri

Matin

Tosefsky

et al. 2021

Preprint

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Dynamic protein S-palmitoylation is critical for neuronal function, development, and synaptic plasticity. Activity-dependent changes in palmitoylation have been observed for several neuronal substrates, however a full characterization of the activity-regulated palmitoylome is lacking. Here, we use an unbiased approach to identify differentially palmitoylated proteins in the mouse hippocampus following context-dependent fear conditioning. Of the 121 differentially palmitoylated proteins identified 63 were synaptic proteins, while others were associated with metabolic functions, cytoskeletal organization, and signal transduction. The vast majority of synaptic proteins exhibited increased palmitoylation following fear conditioning, whereas proteins that exhibited decreased palmitoylation were predominantly associated with metabolic processes. We show a link between dynamic palmitoylation and synapse plasticity by demonstrating that the palmitoylation of one of our identified proteins, PRG-1/LPPR4, is essential for activity-induced insertion of AMPA receptors into the postsynaptic membrane. Together, this study identifies networks of synaptic proteins whose dynamic palmitoylation may play a central role in learning and memory.SUMMARYThis study identifies networks of proteins that undergo dynamic post-translational palmitoylation in response to fear conditioning and demonstrates that palmitoylation of one of these proteins is essential for synapse plasticity. Together, this illustrates the importance of palmitoylation in learning/memory and synapse plasticity.

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Section: Resultsmentioning

confidence: 68%

Synaptic Activity-Dependent Changes in the Hippocampal Palmitoylome

Nasseri

Matin

Tosefsky

et al. 2021

Preprint

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“…Various long-chain fatty acids can bind, whereas shortchain analogs do not bind at all; this pattern is commonly found for the acylation of proteins (Gordon et al, 1991;Berthiaume et al, 1994). The spin label experiments provide additional information on the nature of the acylated state.…”

Section: Discussionmentioning

confidence: 95%

Autocatalytic Acylation of Phospholipase-like Myotoxins

Pedersen

Lomonte²,

Massoud³

et al. 1995

Biochemistry

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Several snake venoms contain a phospholipase A2 in which position 49 in the active site is occupied by a lysine or a serine instead of the aspartate residue normally found. Although these proteins do not bind Ca2+ and are devoid of catalytic activity, they are still highly specific myotoxins and have recently been shown to induce membrane leakage by a new type of cytolytic mechanism. Three of these toxins, myotoxin II from Bothrops asper, ammodytin L from Vipera ammodytes, and the K49 protein from Agkistrodon piscivorus piscivorus, were examined for their interaction with fatty acids and were found to bind long-chain fatty acids covalently by a rapid, spontaneous, autocatalytic process. The fatty acids could be released by treatment with 1 M NH2OH or NaOH, but not with 1 M NaCl or by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Electron spin resonance studies using spin-labeled fatty acids showed that only the carboxyl headgroup of the fatty acid was linked to protein amino acid, the carbon chain had free mobility and did not bind tightly to the protein surface. Stearic acid methyl esters and short-chain fatty acids did not bind to the toxins. Acylated myotoxins bound to the surface of liposomes and isolated muscle membranes, with the fatty acid moiety inserted into the lipid bilayer and possibly acting as an anchor. The phospholipase-like myotoxins represent the first group of proteins able to undergo acylation by spontaneous reaction with free fatty acids.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…In rodents, acot1, acot2, acot3 (Acyl-CoA thioesterase), and acaa1b (Acetyl-Coenzyme A acyltransferase 1), enzymes responsible for acyl-Coa and acetyl-CoA hydrolysis were upregulated [64]. Although the role of Acot enzymes in fatty acid metabolism is not fully understood, they are considered a key element in maintaining an optimal level of fatty acids' beta-oxidation [65]. In fish, we noticed a possible activation of these lipids' pathways.…”

Section: Discussionmentioning

confidence: 99%

Dietary Soy Impact on Host Transcriptome Profile—A Review

et al. 2021

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Whether eaten, drank, or taken in the form of supplements, soybean has been a part of the human diet for centuries. The dietary use of soybean has been extensively proven to be beneficial for human health, protecting against a wide range of chronic diseases. However, our knowledge regarding the impact of soy intake on global gene expression is still incomplete. The present review summarizes and compares data describing the transcriptional changes in several tissues from two different phyla (fish and mammals) upon soybean diet supplementation. We performed comparative STRING-based pathway enrichment analysis of both individual and aggregated soy-induced transcriptome data in fish and mammals and identified the signaling pathways common between the two datasets. We hypothesize that these pathways represent a conserved transcriptome response to the soy-enriched dietary challenge.

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Regulation of enzymatic activity by active site fatty acylation. A new role for long chain fatty acid acylation of proteins.

Cited by 69 publications

References 35 publications

Synaptic Activity-Dependent Changes in the Hippocampal Palmitoylome

Synaptic Activity-Dependent Changes in the Hippocampal Palmitoylome

Autocatalytic Acylation of Phospholipase-like Myotoxins

Dietary Soy Impact on Host Transcriptome Profile—A Review

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