Multiple interactions between pituitary hormones and the mannose receptor

Simpson, Daniel Z.; Hitchen, Paul G.; Elmhirst, Elizabeth L.; Taylor, Maureen E.

doi:10.1042/0264-6021:3430403

Cited by 23 publications

(18 citation statements)

References 9 publications

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“…Expression and Purification of Mannose Receptor-Production of Chinese hamster ovary cell lines expressing the extracellular region of the mannose receptor (MMR-S) and a fragment containing only the eight CRDs (MMR1-8) has been described previously (18). Both cell lines were maintained in ␣-minimal essential medium without nucleosides or deoxyribonucleosides, supplemented with 10% dialyzed fetal calf serum and 0.5 M methotrexate.…”

Section: Methodsmentioning

confidence: 99%

An Extended Conformation of the Macrophage Mannose Receptor

Napper

Dyson²,

Taylor

2001

Journal of Biological Chemistry

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The macrophage mannose receptor mediates phagocytosis of pathogenic microorganisms and endocytosis of potentially harmful soluble glycoproteins by recognition of their defining carbohydrate structures. The mannose receptor is the prototype for a family of receptors each having an extracellular region consisting of 8 -10 domains related to C-type carbohydrate recognition domains (CRDs), a fibronectin type II repeat and an N-terminal cysteine-rich domain. Hydrodynamic analysis and proteolysis experiments performed on fragments of the extracellular region of the receptor have been used to investigate its conformation. Size and shape parameters derived from sedimentation and diffusion coefficients indicate that the receptor is a monomeric, elongated and asymmetric molecule. Proteolysis experiments indicate the presence of close contacts between several pairs of domains and exposed linker regions separating CRDs 3 and 6 from their neighboring domains. Hydrodynamic coefficients predicted for modeled receptor conformations are consistent with an extended conformation with close contacts between three pairs of CRDs. The N-terminal cysteine-rich domain and the fibronectin type II repeat appear to increase the rigidity of the molecule. The rigid, extended conformation of the receptor places domains with different functions at distinct positions with respect to the membrane.The mannose receptor of macrophages and liver endothelial cells is the best characterized member of a family of multidomain cell-surface receptors (1). Each member of the family shares the same overall domain organization, with an extracellular region consisting of an N-terminal cysteine-rich domain followed by a fibronectin type II repeat and 8 or 10 domains related in sequence to the C-type carbohydrate-recognition domains (CRDs) 1 of animal lectins. The mannose receptor and one other member of the family, endothelial receptor Endo-180, are true C-type lectins, binding carbohydrates in a Ca 2ϩ -dependent manner (2, 3). In contrast, the C-type lectinlike domains of the M-type phospholipase A 2 receptor and the dendritic cell receptor DEC-205 do not contain the conserved residues necessary for Ca 2ϩ -dependent sugar binding, and these two receptors do not bind carbohydrates (4 -6). Each of the receptors mediates endocytosis, but physiological ligands have only been identified for the mannose receptor and the phospholipase A 2 receptor.The mannose receptor acts as a molecular scavenger, binding and internalizing pathogenic microorganisms and potentially harmful glycoproteins (7,8). The multiple domains in the extracellular region of the receptor allow recognition of a diverse range of glycoconjugate ligands. Several of the eight C-type CRDs are involved in Ca 2ϩ -dependent recognition of terminal mannose, N-acetylglucosamine or fucose residues on the surfaces of microorganisms or on the oligosaccharides of endogenous glycoproteins (9, 10). The receptor plays a role in the immune response against pathogens such as Mycobacterium tuberculosis and Pneumocyst...

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Section: Methodsmentioning

confidence: 99%

An Extended Conformation of the Macrophage Mannose Receptor

Napper

Dyson²,

Taylor

2001

Journal of Biological Chemistry

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“…Similarly, rhTSH produced in insect cells containing mannose-rich glycans was found to be of high activity but displayed a rapid clearance because it was eliminated through a mannose-specific receptor. Studies by Simpson et al (178) indicated that SO 4 -4GalNAc-containing LH and TSH bind to the NH 2 -terminal cysteine-rich domain of the macrophage mannose receptor, distinct from the mannose binding site. Thus sialic acid and its derivatives thus appeared optimal terminal sugar candidates to create long-lasting glycoforms of rhTSH drug.…”

Section: Metabolic Clearancementioning

confidence: 99%

Thyroid-Stimulating Hormone and Thyroid-Stimulating Hormone Receptor Structure-Function Relationships

Szkudlinski

Frémont²,

Ronin³

et al. 2002

Physiological Reviews

402

256

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This review focuses on recent advances in the structure-function relationships of thyroid-stimulating hormone (TSH) and its receptor. TSH is a member of the glycoprotein hormone family constituting a subset of the cystine-knot growth factor superfamily. TSH is produced by the pituitary thyrotrophs and released to the circulation in a pulsatile manner. It stimulates thyroid functions using specific membrane TSH receptor (TSHR) that belongs to the superfamily of G protein-coupled receptors (GPCRs). New insights into the structure-function relationships of TSH permitted better understanding of the role of specific protein and carbohydrate domains in the synthesis, bioactivity, and clearance of this hormone. Recent progress in studies on TSHR as well as studies on the other GPCRs provided new clues regarding the molecular mechanisms of receptor activation. Such advances are a result of extensive site-directed mutagenesis, peptide and antibody approaches, detailed sequence analyses, and molecular modeling as well as studies on naturally occurring gain- and loss-of-function mutations. This review integrates expanding information on TSH and TSHR structure-function relationships and summarizes current concepts on ligand-dependent and -independent TSHR activation. Special emphasis has been placed on TSH domains involved in receptor recognition, constitutive activity of TSHR, new insights into the evolution of TSH bioactivity, and the development of high-affinity TSH analogs. Such structural, physiological, pathophysiological, evolutionary, and therapeutic implications of TSH-TSHR structure-function studies are frequently discussed in relation to concomitant progress made in studies on gonadotropins and their receptors.

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“…Following a single transmembrane domain a short cytoplasmic domain directs the trafficking of these receptors between the plasma membrane and the endosomal apparatus. The MR is unique within the family in that its CysR domain has a lectin activity, being able to bind sulfated oligosaccharides such as those present on the pituitary hormones lutropin and thyrotropin (14,15). Conversely, the sequence analysis of the FNII predicts that all family members will bind collagen (2).…”

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Structural Model for the Mannose Receptor Family Uncovered by Electron Microscopy of Endo180 and the Mannose Receptor

Boskovic

Arnold

Stilion

et al. 2006

Journal of Biological Chemistry

107

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The mannose receptor family comprises four members in mammals, Endo180 (CD280), DEC-205 (CD205), phospholipase A 2 receptor (PLA 2 R) and the mannose receptor (MR, CD206), whose extracellular portion contains a similar domain arrangement: an N-terminal cysteine-rich domain (CysR) followed by a single fibronectin type II domain (FNII) and 8 -10 C-type lectin-like domains (CTLDs). These proteins mediate diverse functions ranging from extracellular matrix turnover through collagen uptake to homeostasis and immunity based on sugar recognition. Endo180 and the MR are multivalent transmembrane receptors capable of interacting with multiple ligands; in both receptors FNII recognizes collagens, and a single CTLD retains lectin activity (CTLD2 in Endo180 and CTLD4 in MR). It is expected that the overall conformation of these multivalent molecules would deeply influence their function as the availability of their binding sites could be altered under different conditions. However, conflicting reports have been published on the three-dimensional arrangement of these receptors. Here, we have used single particle electron microscopy to elucidate the three-dimensional organization of the MR and Endo180. Strikingly, we have found that both receptors display distinct threedimensional structures, which are, however, conceptually very similar: a bent and compact conformation built upon interactions of the CysR domain and the lone functional CTLD. Biochemical and electron microscopy experiments indicate that, under a low pH mimicking the endosomal environment, both MR and Endo180 experience large conformational changes. We propose a structural model for the mannose receptor family where at least two conformations exist that may serve to regulate differences in ligand selectivity.The mannose receptor (MR 4 and CD206), together with Endo180 (also known as the urokinase-type plasminogen activator receptor-associated protein (uPARAP) and CD280), the dendritic cell receptor DEC-205 (CD205) and the M-type phospholipase A 2 receptor (PLA 2 R) encompass the mannose receptor family of endocytic receptors (1, 2). The members of this family are unique within the superfamily of C-type lectins as these alone contain multiple C-type lectin-like domains (CTLDs) within a single polypeptide backbone. All these receptors are recycled between the plasma membrane and the endosomal apparatus and mediate the uptake of extracellular ligands for intracellular delivery (2). Recently, an avian structural homologue of the mammalian mannose receptor family members, FcRY, has been discovered to function as a yolk sac IgY receptor (3).The MR was originally described as a transmembrane receptor that recognized saccharide chains terminating in mannose and designated as the macrophage mannose receptor. Since its expression was found not to be restricted to macrophages, it is now known as MR (2). MR executes important roles in the immune system by functioning as a pattern recognition receptor toward a wide range of pathogens. Other members of the family were found ...

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Multiple interactions between pituitary hormones and the mannose receptor

Cited by 23 publications

References 9 publications

An Extended Conformation of the Macrophage Mannose Receptor

An Extended Conformation of the Macrophage Mannose Receptor

Thyroid-Stimulating Hormone and Thyroid-Stimulating Hormone Receptor Structure-Function Relationships

Structural Model for the Mannose Receptor Family Uncovered by Electron Microscopy of Endo180 and the Mannose Receptor

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