9.B.39.1.1
CD36 (cluster of differentiation 36) antigen; once thought to be a plasma membrane fatty acid transporter of 472 aas and 2 TMSs, N- and C-terminal (Schwenk et al. 2010). Also called the scavenger receptor protein (SR-B2) as it binds many ligands including both Gram-positive and Gram-negative bacteria; it plays a role in immune development (Liu et al. 2016). Direct interaction of CD36 with glycerol phospholipids has been demonstrated (Tsuzuki et al. 2017). CD36 plays a role in the perception of specific odour-active volatile compounds including oleic aldehyde (cis-9-octadecenal), in the nasal cavity (Lee et al. 2017). Jay et al. 2020 have concluded that LCFAs diffuse rapidly across biological membranes and do not require an active protein transporter such as CD36 for their transmembrane movement. CD36 (SR-B2) may be a target to treat lipid overload-induced  cardiac dysfunction (Glatz et al. 2020). CD36 is released into the circulation (cCD36) of WT mice in response to tail-vein injection of oxPCCD36. The presence of cCD36 in hyperlipidemia revealed  a link between cCD36 and oxidized phospholipids generated under oxidative stress and low-grade inflammation associated with hyperlipidemia (Biswas et al. 2021). Inhibition of fatty acid translocase (FAT/CD36) palmitoylation enhances hepatic fatty acid beta-oxidation by increasing its localization to mitochondria and interaction with long-chain acyl-CoA synthetase 1 (Zeng et al. 2022). CD36 expression is related to human epidermal growth factor receptor 2 (HER2)-positive breast cancer (Ligorio et al. 2022).  A CD36 transmembrane domain peptide interrupts CD36 interactions with membrane partners on macrophages and inhibits atherogenic functions (Huang et al. 2023). CD36 is a transmembrane glycoprotein receptor for oxidized low density lipoprotein (LDL) and other endogenous danger signals and promotes athero-thrombotic processes. CD36 associates physically with other transmembrane proteins, including integrins, tetraspanins, and toll-like receptors, which modulate CD36-mediated cell signaling. The CD36 N-terminal TMS contains a GXXXG sequence motif that mediates protein-protein interactions with many membrane proteins. Huang et al. 2023 thus hypothesized that the nTMS is involved in CD36 interactions with other membrane proteins. CD36 interactions with partner cell surface proteins on murine peritoneal macrophages were detected with an immunofluorescence-based proximity ligation cross linking assay (PLA) and confirmed by immunoprecipitation/immunoblot. Prior to performing these assays, cells were incubated with a synthetic 29 amino acid peptide containing the 22 amino acids of CD36 nTMD or a control peptide in which the glycine residues in GXXXG motif were replaced by valines. Macrophages were preincubated with peptides and then treated with oxLDL to assess LDL uptake and other properties. CD36 nTMD peptide treated cells compared to untreated or control peptide treated cells showed decreased CD36 surface associations with tetraspanin CD9 (TC# 8.A.40.1.9) and ameliorated pathologically important CD36 mediated responses to oxLDL, including uptake of DiI-labeled oxLDL, foam cell formation, ROS generation, and inhibition of migration (Huang et al. 2023). CD36 may play a role in transmembrane transport and tissue partition of per- and polyfluoroalkyl substances (PFASs) in mice (Jia et al. 2023). CD36 preferentially mediates intestinal absorption of dietary Z-astaxanthin and especially the 9- Z-isomer due to higher binding affinity (Zhang et al. 2024).