Abstract
CD36 is a transmembrane glycoprotein receptor for oxidized low density lipoprotein
(LDL) and other endogenous danger signals and promotes athero-thrombotic processes.
CD36 has been shown to associate physically with other transmembrane proteins, including
integrins, tetraspanins, and toll-like receptors, which modulate CD36-mediated cell
signaling. The CD36 N-terminal transmembrane domain (nTMD) contains a GXXXG sequence
motif that mediates protein-protein interactions in many membrane proteins. We thus
hypothesized that the nTMD 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
acid of CD36 nTMD or a control peptide in which the glycine residues in GXXXG motif
were replaced by valines. In functional experiments, macrophages were preincubated
with peptides and then treated with oxLDL to assess LDL uptake, foam cell formation,
ROS formation and cell migration. CD36 nTMD peptide treated cells compared to untreated
or control peptide treated cells showed decreased CD36 surface associations with tetraspanin
CD9 and ameliorated pathologically important CD36 mediated responses to oxLDL, including
uptake of DiI-labeled oxLDL, foam cell formation, ROS generation, and inhibition of
migration.
Abbreviations:
LDL (low density lipoprotein), oxLDL (oxidized low density lipoprotein), nTMD (N-terminal transmembrane domain), ROS (reactive oxygen species), SDS-PAGE (sodium dodecyl sulfate–polyacrylamide gel electrophoresis), DiI (1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate), MAPK (mitogen activated protein kinase), PLA (proximity ligation assay)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: October 26, 2022
Accepted:
October 20,
2022
Received in revised form:
October 14,
2022
Received:
April 15,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2022 Elsevier Inc. All rights reserved.
