CD 206: MANNOSE RECEPTOR CATEGORY: RECEPTORS & MOLECULES CD 206: Mannose Receptor Luisa Martinez-Pomares, University of Nottingham, UK The mannose receptor is a member of the c-type lectin family of receptors. It is expressed by macrophages, dendritic cells and hepatic and lymphatic endothelia. Expression in macrophages and dendritic cells is regulated by microbial products and cytokines. The mannose receptor is an endocytic receptor; it constantly recycles between the plasma membrane and the early endocytic compartment. Because of its ability to recognise molecules of endogenous and microbial origin it is thought to have a major role in homeostasis and immunity. Domain structure of the mannose receptor: CR: Cysteine-rich domain Recognises sulphated carbohydrates terminated in SO4-(3)-Gal- or SO4-(3/4)-GalNAc-. Binding to ligands improved by protein multimerisation. FNII: Fibronectin type II domain Recognises native and denatured collagens. Binds Collagen I, II, III, IV and (weakly) V.. Requires protein multimerisation for binding. CR © The copyright for this work resides with the author FNII CTLD: C-type lectin-like domain Through these domains MR binds complex carbohydrates terminated in mannose, fucose or N-acetyl-glucosamine. Cytoplasmic tail Intracellular targeting mediated by a tyrosine-based motif in the cytoplasmic tail, similar to the one found in the low density lipoprotein (LDL)-receptor (FENTLY). CTLD CTLD-4: Is a C-type lectin carbohydrate recognition domain. The only CTLD able to bind carbohydrate in isolation. Requires Ca2+ and neutral pH. Recycling from early endosomes is mediated by the di-aromatic motif comprised of the tyrosine present in the endocytosis motif and an adjacent phenylalanine. Mannose receptor ligands: Sulphated glycoprotein hormones from anterior pituitary. Chondroitin sulphate. Sulphated Lewisx/a. SorLA/LR11 in mouse kidney. CD45 and sialoadhesin in mouse secondary lymphoid organs. CR doman ligands FNII domain ligands CTLD ligands Microbial: Mycobacterium tuberculosis HIV Candida albicans Pneumocystis carinii Klebsiella pneumoniae LPS Streptococcus pneumoniae CPS Dengue virus Collagens Endogenous: Lysosomal hydrolases Myeloperoxidase Tissue plasminogen activator Thyroglobulin Ligands in secretory organs