ASGR1 and Its Enigmatic Relative, CLEC10A

Abstract

<jats:p>The large family of C-type lectin (CLEC) receptors comprises carbohydrate-binding proteins that require Ca2+ to bind a ligand. The prototypic receptor is the asialoglycoprotein receptor-1 (ASGR1, CLEC4H1) that is expressed primarily by hepatocytes. The early work on ASGR1, which is highly specific for N-acetylgalactosamine (GalNAc), established the foundation for understanding the overall function of CLEC receptors. Cells of the immune system generally express more than one CLEC receptor that serve diverse functions such as pathogen-recognition, initiation of cellular signaling, cellular adhesion, glycoprotein turnover, inflammation and immune responses. The receptor CLEC10A (C-type lectin domain family 10 member A, CD301; also called the macrophage galactose-type lectin, MGL) contains a carbohydrate-recognition domain (CRD) that is homologous to the CRD of ASGR1, and thus, is also specific for GalNAc. CLEC10A is most highly expressed on immature DCs, monocyte-derived DCs, and alternatively activated macrophages (subtype M2a) as well as oocytes and progenitor cells at several stages of embryonic development. This receptor is involved in initiation of TH1, TH2, and TH17 immune responses and induction of tolerance in naïve T cells. Ligand-mediated endocytosis of CLEC receptors initiates a Ca2+ signal that interestingly has different outcomes depending on ligand properties, concentration, and frequency of administration. This review summarizes studies that have been carried out on these receptors.</jats:p>

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“…7 ASGR is a marker of hepatocyte and highly expresses in the liver parenchymal cells at their plasma membrane, responsible for the clearance of glycoproteins bearing N-linked glycans terminating with the structure Galβ1, 3GalNAc from the hepatocyte. 25 ASGR consists of two subunits ASGR1 and ASGR2. EPCAM is a marker of bile duct cells.…”

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“…We also observed that MGL-1 deficiency leads to downregulation of the related gene Asgr1, which encodes the asialoglycoprotein receptor 1 (ASGR1 and CLEC4H1). Like MGL-1, ASGR1 binds to serum proteins with exposed galactose or N-acetyl-galactosamine residues and targets them to the lysosome for degradation (60). Further investigation is needed to determine whether ASGR1 or other pattern recognition systems are differentially regulated by MGL-1 and the potential impact on immune outcomes.…”

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“…Another potential receptor is ASGR1 (C-type lectin, CLEC), a subunit of the asialoglycoprotein receptor, a transmembrane protein that is responsible for recognizing terminal galactose or N -acetylgalactosamine residues exposed after sialic acid is lost [ 53 , 54 ]. This receptor was found to bind RBD with a K D of about 95 nM, which is substantially higher than in the case of ACE2 or Krm1.…”