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Review
. 2020 Oct 28:8:600368.
doi: 10.3389/fcell.2020.600368. eCollection 2020.

Protein Palmitoylation in Leukocyte Signaling and Function

Xiaoyuan Yang  1 , Victor Chatterjee  1 , Yonggang Ma  1 , Ethan Zheng  1 , Sarah Y Yuan  1   2
Affiliations
Review

Protein Palmitoylation in Leukocyte Signaling and Function

Xiaoyuan Yang et al. Front Cell Dev Biol. .

Abstract

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.

Keywords: DHHC palmitoyl transferases; leukocyte behaviors; leukocyte function/activation; palmitoylation; protein function; signal transduction.

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Figures

FIGURE 1
FIGURE 1
Protein palmitoylation dynamically regulates protein function and signal transduction. The reversible attachment of palmitic acid affects protein function in many ways: (a) palmitoylation alters the conformation or structure of a protein (e.g., the fourth intracellular loop of GPCRs that is formed by inserting palmitate into the plasma membrane); (b) palmitoylation mediates protein intracellular trafficking and ensures stable membrane localization of proteins; (c) palmitoylation stabilizes proteins by preventing misfolding and ubiquitination-mediated degradation; (d) palmitoylation facilitates protein-protein interaction directly and indirectly. In addition, the palmitoylation and de-palmitoylation cycle has critical impact on signal transduction (upper right region circled by red dash line): (e) many signaling proteins require palmitoylation for their translocation into lipid rafts. (f) De-palmitoylation mediates receptor desensitization following activation by promoting the phosphorylation of receptors or the translocation of membrane signaling proteins to cytoplasm. Images of proteins and organelles were obtained from Smart Servier Medical Art (https://smart.servier.com).
FIGURE 2
FIGURE 2
The impact of protein palmitoylation on leukocyte signaling and function. Protein palmitoylation modulates various functions of leukocytes by altering the activities of palmitoylated proteins in different subtypes of leukocytes. Besides, palmitoylation also indirectly affects leukocyte behaviors through regulating the function of endothelial cells. Palmitoylated proteins involved in the particular function are listed in parentheses. Images of cells and proteins were obtained from Smart Servier Medical Art (https://smart.servier.com).
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