Insights Into Protein S-Palmitoylation in Synaptic Plasticity and Neurological Disorders: Potential and Limitations of Methods for Detection and Analysis

S-palmitoylation (S-PALM) is a lipid modification that involves the linkage of a fatty acid chain to cysteine residues of the substrate protein. This common posttranslational modification (PTM) is unique among other lipid modifications because of its reversibility. Hence, like phosphorylation or ubi...

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Main Authors: Monika Zaręba-Kozioł, Izabela Figiel, Anna Bartkowiak-Kaczmarek, Jakub Włodarczyk
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-05-01
Series:Frontiers in Molecular Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fnmol.2018.00175/full
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author Monika Zaręba-Kozioł
Izabela Figiel
Anna Bartkowiak-Kaczmarek
Jakub Włodarczyk
author_facet Monika Zaręba-Kozioł
Izabela Figiel
Anna Bartkowiak-Kaczmarek
Jakub Włodarczyk
author_sort Monika Zaręba-Kozioł
collection DOAJ
description S-palmitoylation (S-PALM) is a lipid modification that involves the linkage of a fatty acid chain to cysteine residues of the substrate protein. This common posttranslational modification (PTM) is unique among other lipid modifications because of its reversibility. Hence, like phosphorylation or ubiquitination, it can act as a switch that modulates various important physiological pathways within the cell. Numerous studies revealed that S-PALM plays a crucial role in protein trafficking and function throughout the nervous system. Notably, the dynamic turnover of palmitate on proteins at the synapse may provide a key mechanism for rapidly changing synaptic strength. Indeed, palmitate cycling on postsynaptic density-95 (PSD-95), the major postsynaptic density protein at excitatory synapses, regulates the number of synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) and thus affects synaptic transmission. Accumulating evidence suggests a relationship between impairments in S-PALM and severe neurological disorders. Therefore, determining the precise levels of S-PALM may be essential for understanding the ways in which this PTM is regulated in the brain and controls synaptic dynamics. Protein S-PALM can be characterized using metabolic labeling methods and biochemical tools. Both approaches are discussed herein in the context of specific methods and their advantages and disadvantages. This review clearly shows progress in the field, which has led to the development of new, more sensitive techniques that enable the detection of palmitoylated proteins and allow predictions of potential palmitate binding sites. Unfortunately, one significant limitation of these approaches continues to be the inability to use them in living cells.
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spelling doaj.art-aacc10894bfb4d648dc55db5685298882022-12-21T22:51:45ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992018-05-011110.3389/fnmol.2018.00175333110Insights Into Protein S-Palmitoylation in Synaptic Plasticity and Neurological Disorders: Potential and Limitations of Methods for Detection and AnalysisMonika Zaręba-KoziołIzabela FigielAnna Bartkowiak-KaczmarekJakub WłodarczykS-palmitoylation (S-PALM) is a lipid modification that involves the linkage of a fatty acid chain to cysteine residues of the substrate protein. This common posttranslational modification (PTM) is unique among other lipid modifications because of its reversibility. Hence, like phosphorylation or ubiquitination, it can act as a switch that modulates various important physiological pathways within the cell. Numerous studies revealed that S-PALM plays a crucial role in protein trafficking and function throughout the nervous system. Notably, the dynamic turnover of palmitate on proteins at the synapse may provide a key mechanism for rapidly changing synaptic strength. Indeed, palmitate cycling on postsynaptic density-95 (PSD-95), the major postsynaptic density protein at excitatory synapses, regulates the number of synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) and thus affects synaptic transmission. Accumulating evidence suggests a relationship between impairments in S-PALM and severe neurological disorders. Therefore, determining the precise levels of S-PALM may be essential for understanding the ways in which this PTM is regulated in the brain and controls synaptic dynamics. Protein S-PALM can be characterized using metabolic labeling methods and biochemical tools. Both approaches are discussed herein in the context of specific methods and their advantages and disadvantages. This review clearly shows progress in the field, which has led to the development of new, more sensitive techniques that enable the detection of palmitoylated proteins and allow predictions of potential palmitate binding sites. Unfortunately, one significant limitation of these approaches continues to be the inability to use them in living cells.https://www.frontiersin.org/article/10.3389/fnmol.2018.00175/fullS-palmitoylationsynapseneurodegenerative diseasesmetabolic labelingbiochemical methodssynaptic plasticity
spellingShingle Monika Zaręba-Kozioł
Izabela Figiel
Anna Bartkowiak-Kaczmarek
Jakub Włodarczyk
Insights Into Protein S-Palmitoylation in Synaptic Plasticity and Neurological Disorders: Potential and Limitations of Methods for Detection and Analysis
Frontiers in Molecular Neuroscience
S-palmitoylation
synapse
neurodegenerative diseases
metabolic labeling
biochemical methods
synaptic plasticity
title Insights Into Protein S-Palmitoylation in Synaptic Plasticity and Neurological Disorders: Potential and Limitations of Methods for Detection and Analysis
title_full Insights Into Protein S-Palmitoylation in Synaptic Plasticity and Neurological Disorders: Potential and Limitations of Methods for Detection and Analysis
title_fullStr Insights Into Protein S-Palmitoylation in Synaptic Plasticity and Neurological Disorders: Potential and Limitations of Methods for Detection and Analysis
title_full_unstemmed Insights Into Protein S-Palmitoylation in Synaptic Plasticity and Neurological Disorders: Potential and Limitations of Methods for Detection and Analysis
title_short Insights Into Protein S-Palmitoylation in Synaptic Plasticity and Neurological Disorders: Potential and Limitations of Methods for Detection and Analysis
title_sort insights into protein s palmitoylation in synaptic plasticity and neurological disorders potential and limitations of methods for detection and analysis
topic S-palmitoylation
synapse
neurodegenerative diseases
metabolic labeling
biochemical methods
synaptic plasticity
url https://www.frontiersin.org/article/10.3389/fnmol.2018.00175/full
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AT annabartkowiakkaczmarek insightsintoproteinspalmitoylationinsynapticplasticityandneurologicaldisorderspotentialandlimitationsofmethodsfordetectionandanalysis
AT jakubwłodarczyk insightsintoproteinspalmitoylationinsynapticplasticityandneurologicaldisorderspotentialandlimitationsofmethodsfordetectionandanalysis