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Samiksha Sardana1,2, Anneroos E Nederstigt1,2, Marc P Baggelaar1,2
1Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Padualaan 8, Utrecht 3584 CH, The Netherlands.
Journal of Proteome Research
|June 9, 2023
Summary
S-palmitoylation, a key lipid modification in neurons, is crucial for neurodevelopment. This study identified hundreds of S-palmitoylated proteins during neuronal differentiation, revealing its significant role in this process.
Area of Science:
- Neuroscience
- Biochemistry
- Cell Biology
Background:
- S-palmitoylation, the attachment of fatty acids to cysteines, is abundant in neurons and linked to neurodevelopment and neurodegenerative diseases.
- Understanding S-palmitoylation's role in neurodevelopment is hindered by technological challenges in analyzing this hydrophobic modification.
Purpose of the Study:
- To identify S-palmitoylated proteins and sites during retinoic acid-induced neuronal differentiation of SH-SY5Y cells.
- To investigate the role of S-palmitoylation in neuronal development using advanced proteomic techniques.
Main Methods:
- Utilized two orthogonal methods: acyl-biotin exchange (ABE) and lipid metabolic labeling (LML).
- Analyzed S-palmitoylation changes during retinoic acid-induced neuronal differentiation in SH-SY5Y cells.
Main Results:
- Identified 2002 putative S-palmitoylated proteins, with 650 confirmed by both methods.
- Detected significant changes in S-palmitoylated protein abundance, particularly in pathways vital for neuronal differentiation (e.g., RET signaling, SNARE exocytosis, cell adhesion).
Conclusions:
- Parallel application of ABE and LML successfully identified high-confidence S-palmitoylated proteins during neuronal differentiation.
- S-palmitoylation plays a significant role in the processes underlying neuronal differentiation.