Abstract
Macrophages are present in all tissues within our body, where they promote tissue homeostasis by responding to microenvironmental triggers, not only through clearance of pathogens and apoptotic cells but also via trophic, regulatory, and repair functions. To accomplish these divergent functions, tremendous dynamic fine-tuning of their physiology is needed. Emerging evidence indicates that S-palmitoylation, a reversible post-translational modification that involves the linkage of the saturated fatty acid palmitate to protein cysteine residues, directs many aspects of macrophage physiology in health and disease. By controlling protein activity, stability, trafficking, and protein–protein interactions, studies identified a key role of S-palmitoylation in endocytosis, inflammatory signaling, chemotaxis, and lysosomal function. Here, we provide an in-depth overview of the impact of S-palmitoylation on these cellular processes in macrophages in health and disease. Findings discussed in this review highlight the therapeutic potential of modulators of S-palmitoylation in immunopathologies, ranging from infectious and chronic inflammatory disorders to metabolic conditions.
Highlights
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Noland et al demonstrated that S-palmitoylation controls folding and stability of TEAD family transcription factors [17,18], which are involved in cell growth and differentiation
Our unpublished findings indicate that zinc-finger and aspartate-histidinehistidine-cysteine (zDHHC) and acylprotein thioesterases (APTs) have divergent cellular and tissular distributions, and few studies showed specific subcellular locations of these enzymes [13,22,31,32]. With respect to the latter, the majority of zDHHCs are localized in both the endoplasmic reticulum and Golgi apparatus, which are the primary sites of protein palmitoylation
Summary
Cellular proteins undergo numerous post-translational modifications that extend and regulate protein and, thereby, cellular physiology Some of these modifications, phosphorylation, and ubiquitination, in particular, have been extensively studied and characterized in the context of cellular function in health and disease [1]. N-myristoylation is characterized by the addition of myristic acid, a 14-carbon unsaturated fatty acid, to the alpha-amino group of an N-terminal glycine residue of a wide range of substrate proteins. It plays a vital role in signal transduction, protein stability, and the localization of proteins to membranes [7,8]. We summarize and discuss the current knowledge on the impact of S-palmitoylation, one of the most common forms of protein lipidation, on protein signaling, translocation, and interactions in innate immune cells, macrophages in particular
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