Selenoprotein K contributes to CD36 subcellular trafficking in hepatocytes by accelerating nascent COPII vesicle formation and aggravates hepatic steatosis

SELENOK-dependent CD36 palmitoylation regulates microglial functions and Aβ phagocytosis

“…As no direct and effective targets or mechanisms were identified at the transcriptomic level, we shifted our focus to exploring the mechanisms from the perspective of microglial Aβ phagocytosis. Microglial Aβ phagocytosis is reliant on specific receptors [ [49] , [50] , [51] , [52] , [53] ], including CD36, which is not only a critical Aβ receptor but also a palmitoylated protein modulated by SELENOK [ 54 , 55 ]. However, this has been shown only in macrophages, with no direct evidence of the regulation of CD36 palmitoylation by SELENOK in the microglia or brain.…”

“…Palmitoylation typically governs protein transport and membrane localization and plays a pivotal role in CD36 functionality [ 59 , 60 ]. Previous studies indicate that palmitoylation assists CD36 in localizing within the cellular membrane system, facilitating its transport to the cell membrane [ 54 , 61 ]. Evidently, CD36 localization in the microglial membrane is crucial for it to recognize and bind Aβ, thus enhancing microglial phagocytosis and Aβ degradation [ 62 ].…”

“…Therefore, CD36 trafficking from the ER to the plasma membrane is orchestrated by a cascade of DHHC enzymes, with DHHC6 potentially directly influencing its transport to the Golgi. Recent studies exploring the effect of SELENOK on CD36 transport in hepatocytes have affirmed this process [ 54 ].…”

The role of s-palmitoylation in neurological diseases: implication for zDHHC family

“…Palmitoylation may also enhance the tethering of the ER to the PM by Junctophilins ( Jiang et al, 2019 ). SelK (Selenoprotein K) accelerates the transport of the palmitoylated fatty acid transporter enzyme CD36 from the ER to the Golgi, thereby promoting the PM distribution of CD36 in vivo and in vitro ( You et al, 2022 ). zDHHC6 present on the ER membrane forms a SelK/zDHHC6 complex with SelK, an ER transmembrane protein that has been shown to be important for ER stress and calcium-dependent signaling, which catalyzes the transfer of fatty acids, such as palmitic acid, to the cysteine residues of target proteins to initiate palmitoylation.…”

Metal-Binding Proteins Cross-Linking with Endoplasmic Reticulum Stress in Cardiovascular Diseases

“…However, SelK has also been reported to promote the development of atherosclerosis. Moreover, SelK acts as a cofactor of DHHC6 (the letters represent the amino acids aspartic acid, histidine, histidine, and cysteine in the catalytic domain) in the ER to regulate the palmitoylation of triphosphate receptor and CD36 in immune cells and macrophages, respectively [61]. Increased SelK gene expression promotes the subcellular transport of fatty acid transferase (CD36) because CD36 mediates the uptake of long-chain fatty acids in myocardial tissue, so SelK overexpression exacerbates lipid accumulation in cells and promotes foam cell formation and atherosclerosis.…”