Group VI - Macrophage Mannose Receptor Family

Introduction
Sequence alignments: Human Human/Mouse

 

Group VI domain organizationThe mannose receptor group of CTLD-containing cell surface proteins contains four members in both human and mouse.  These type 1 transmembrane proteins have large extracellular domains in which a membrane-distal cysteine-rich domain is followed by a fibronectin type II domain and 8 CTLDs (10 in the dendritic and thymic epithelial cell receptor DEC-205).  The short cytoplasmic domains direct constitutive endocytosis and recycling of these receptors. 

 

The mannose receptor is expressed on macrophages, liver endothelial cells, and some other cell types, and internalizes both endogenous and foreign glycoconjugates for degradation.  The cysteine-rich domain in the mannose receptor is an R-type CRD that clears sulphated glycoprotein hormones from the blood.  Several of the CTLDs participate in the binding of pathogen-related glycoconjugates, and of endogenous glycoproteins secreted from cells as a result of infection or injury.  Internalized pathogens are generally degraded, but the mycobacteria responsible for tuberculosis and leprosy employ the mannose receptor specifically to infect macrophages.  The fibronectin domain of the mannose receptor binds collagen.  Endo180 is expressed on fibroblasts, macrophages, endothelial cells, and foetal bone and cartilage cells.  It also binds collagen and furthermore effects collagen uptake and degradation and promotes fibroblast adhesion and migration in collagen matrices.  Endo180 may participate in collagen matrix remodelling in development, homeostasis, wound healing, and disease, including cancer.  Matrix remodelling involves an extracellular proteolytic system formed by the urokinase plasminogen activator (uPA) and its receptor (uPAR), in which Endo180 is a co-receptor for uPA.  The phospholipase A2 receptor is expressed on alveolar epithelial cells and spleen lymphocytes.  CTLDs in the receptor bind secretory phospholipase A2 enzymes through protein-protein interactions.  Receptor ligation stimulates cell proliferation, migration, and release of hormones, lipid mediators, and cytokines.  The receptor also internalizes ligands and a soluble form competes for ligand binding, thus downregulating the enzymatic and receptor-mediated activities of phospholipase A2s.  DEC-205 internalizes antigens for processing and presentation to T cells by dendritic cells.  It is also expressed in certain epithelia, lymphocytes and endothelial cells, clears apoptotic T cells, and influences cell proliferation and differentiation through association with the IL-4 receptor. 

 

Carbohydrate recognition by both R-type and C-type CRDs is integral to the function of the mannose receptor.  Although only CTLD4 exhibits independent binding to mannose-type sugars, CTLDs 5-7 also contribute to higher affinity binding of multivalent ligands.  CTLD2 in Endo180 also binds mannose-type sugars, but the physiological role of carbohydrate recognition is not known.  The phospholipase A2 receptor and DEC-205 do not bind sugars.

 

Structure of the R-type CRD from the murine mannose receptor with bound 4-O-sulphated GalNAc

The sugar ligand is coloured by atom: black, carbon; red, oxygen; blue, nitrogen; yellow, sulphur.  Protein Data Bank structure ID: 1DQO.

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This page last updated:
Wednesday, 01 January 2014
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Contact information: This site is supported by:
 
Kurt Drickamer
Division of Molecular Biosciences
Faculty of Natural Sciences
Imperial College London
 
Email: k.drickamer@imperial.ac.uk