Insights into binding of S100 proteins to scavenger receptors: class B scavenger receptor CD36 binds S100A12 with high affinity

Abstract

The EF-hand type calcium-binding protein S100A12 exerts numerous intra- and extracellular functions of (patho)physiological relevance. Therefore, receptors of S100A12 are of high interest for research and clinical applications. Beside the extensively studied receptor for advanced glycation endproducts (RAGE), G-protein coupled receptors and more recently, scavenger receptors are suggested to be putative S100A12 receptors. Own findings and further information from the literature predestined CD36, a class B scavenger receptor, as promising candidate. To substantiate or prove against this hypothesis, this study aimed at investigation of interaction of S100A12 and CD36 on molecular and cellular level by the use of surface plasmon resonance (SPR), radio- and fluorescence-tracer-based cell binding, and cell activation experiments. S100A12 revealed binding affinity to CD36 in the low nanomolar range, essentially, at the CD36 thrombospondin-1 binding site. Additionally, S100A12-mediated translocation of CD36 to the membrane and elevation of both CD36 and peroxisome proliferator-activated receptor γ (PPARγ) expression was observed, which suggest a potential regulatory function of S100A12–CD36 interaction.Electronic supplementary materialThe online version of this article (doi:10.1007/s00726-016-2349-2) contains supplementary material, which is available to authorized users.

CD146, from a melanoma cell adhesion molecule to a signaling receptor

“…The secreted S100 proteins bind with several cell-surface receptors, including advanced glycation end products (RAGE), 142 – 146 toll-like receptor 4 (TLR4), 147 CD36, 148 FGFR1, 149 ALCAM, 150 CD68, 151 and ErbB4. 152 However, how the cell-surface receptors mediate extracellular S100 signaling is lacking and how S100 protein secretion is dynamically regulated in biological processes also still remains unknown.…”

CD36 in chronic kidney disease: novel insights and therapeutic opportunities

“…Renal CD36 expression is upregulated by hyperlipidaemia and hyperglycaemia, and patients with chronic kidney disease (CKD), particularly those with diabetic nephropathy, show increased expression of the protein. 12,17 CD36 has multiple ligands, which can be classified as lipid-related ligands, such as (long-chain) fatty acids, 18 oxidized LDL (Ox-LDL), 19,20 and oxidized phospholipids 21 ; and as protein-related ligands, including advanced oxidation protein products (AOPPs), 22 advanced glycation end products (AGEs), 23 thrombospondin-1 (TSP1), TSP2, 24,25 S100 family proteins (S100-A8, S100-A9 26 and S100-A12 27 ), amyloid proteins 28,29 , and the synthetic growth-hormone-releasing peptide family members hexarelin 30 and EP 80317 31 . Apoptotic cells can also act as a ligand for CD36 32 (Table 1).…”

A Review of Selected IBD Biomarkers: From Animal Models to Bedside

“…It is also found in endothelial cells, keratinocytes, and epithelial cells under inflammatory conditions [ 35 ]. S100A12 is known to be a ligand for RAGE [ 36 ], toll-like receptor 4 (TLR4) [ 37 , 38 ], and CD36 (also known as platelet glycoprotein 4) [ 39 , 40 ], which are receptors for advanced glycation end products (AGEs) expressed on monocytes and epithelial cells. S100A12 exists in a variety of forms, including homodimers and hexamers [ 41 ], and binds to the V- or C-type domains (V and C1 domains) of RAGE, which are well known as pattern recognition receptors (PRRs).…”