Disease relevance of Mrc2

• Genetic ablation of uPARAP/Endo180 impaired collagen turnover that is critical to tumor expansion, as evidenced by the abrogation of cellular collagen uptake, tumor fibrosis, and blunted tumor growth [1].
• OBJECTIVE: To investigate the expression of a novel member of the mannose receptor family, Endo180 (also known as uPARAP), and the distribution of Endo180 ligand(s) in the articular cartilage and growth plate of normal CBA mice and STR/ort mice, a well characterized model of spontaneous osteoarthritis [2].

High impact information on Mrc2

• We recently reported that uPARAP/Endo180 can mediate the cellular uptake and lysosomal degradation of collagen by cultured fibroblasts [1].
• Intracellular collagen degradation mediated by uPARAP/Endo180 is a major pathway of extracellular matrix turnover during malignancy [1].
• In the normal murine mammary gland, uPARAP/Endo180 is widely expressed in periductal fibroblast-like mesenchymal cells that line mammary epithelial cells [1].
• Fibroblasts from mice with a targeted deletion in the uPARAP/Endo180 gene displayed a near to complete abrogation of collagen endocytosis [3].
• Resident bone marrow macrophages in hematopoietic clusters have previously been shown to express a novel lectin-like sheep erythrocyte receptor, SER, which mediates binding of unopsonized sheep erythrocytes via recognition of sialylated glycoconjugates and may interact with sialylated ligands on murine bone marrow cells [4].

Biological context of Mrc2

• We have generated mice with a targeted deletion of Endo180 exons 2-6 and show that this mutation results in the efficient expression of a truncated Endo180 protein that lacks the cysteine-rich domain, the FNII domain and CTLD1 [5].
• The presence of intelectin-2 in resistant BALB/c mice, its absence from the susceptible C57BL/10 strain and the kinetics of its up-regulation during T. spiralis infection suggest that this novel lectin may serve a protective role in the innate immune response to parasite infection [6].
• These results suggest that KML-C is a novel lectin related to the cytotoxicity of Korean mistletoe, and that its cytotoxic activity against tumor cells is due to apoptosis mediated by Ca2+/Mg2+ -dependent endonucleases [7].
• A novel lectin derived from silkworm faeces, named NUE, activates phagocytosis of mouse peritoneal macrophages [8].

Anatomical context of Mrc2

• uPARAP/Endo180 is essential for cellular uptake of collagen and promotes fibroblast collagen adhesion [3].
• We conclude that uPARAP/endo180 is critical for targeted delivery of collagen IV to lysosomes for degradation implicating the receptor in normal and malignant extracellular matrix degradation [9].
• Besides bone-forming tissues, uPARAP/Endo180 expression was detected only in a mesenchymal condensation of the midbrain and in the developing lungs [10].
• Endo180, an endocytic recycling glycoprotein related to the macrophage mannose receptor is expressed on fibroblasts, endothelial cells and macrophages and functions as a lectin receptor [11].
• Endo180 is found to be predominantly expressed in vivo and in vitro on fibroblasts, endothelial cells and macrophages, and the distribution and post-translational processing in these cells is consistent with Endo180 functioning to internalize glycosylated ligands from the extracellular milieu for release in an endosomal compartment [11].

Associations of Mrc2 with chemical compounds

• The four members of the mannose receptor family (the mannose receptor, the M-type phospholipase A(2) receptor, DEC-205 and Endo180) share a common extracellular arrangement of an amino-terminal cysteine-rich domain followed by a fibronectin type II (FNII) domain and multiple C-type lectin-like domains (CTLDs) [5].
• We now show that the endocytic transmembrane glycoprotein urokinase plasminogen activator receptor-associated protein (uPARAP/endo180) directs collagen IV for lysosomal delivery and degradation [9].
• A novel lectin was isolated from the leaf skin of "Kidachi Aloe" (Aloe arborescens Miller var. natalensis Berger) by sequential chromatographies on Sephadex G-25 gel filtration, DEAE ion exchange, and Superdex 75 gel filtration columns [12].

Other interactions of Mrc2

• In this study we sequence this novel lectin, termed intelectin-2, and compare expression levels during T. spiralis infection of resistant (BALB/c) with susceptible (C57BL/10) mouse strains [6].
• Genomic Southern blot analyses suggest that Ym1 may represent a member of a novel lectin gene family [13].

Analytical, diagnostic and therapeutic context of Mrc2

• Sequence analysis of Endo180 reveals that the second carbohydrate recognition domain has retained key conserved amino acids found in other functional C-type lectins [11].
• We have purified a soluble version of Endo180 and analysed it by single-particle electron microscopy to obtain a three-dimensional structure of the N-terminal part of the protein at a resolution of 17 A and reveal, for the first time, the interactions between non-adjacent domains in the mannose receptor family [14].
• The remodeled cells were endowed with novel lectin binding profiles as determined by flow cytometry analysis [15].
• We have shown that gene transfer can be accomplished by these novel lectin-targeted molecular conjugate vectors and that lectin binding specificities may serve as a means for potential targeting of cancer cells for the purposes of gene therapy [16].
• A novel lectin having specificity towards a complex glycoprotein asialofetuin was purified from tubers of Arisaema flavum (Schott.) by affinity chromatography on asialofetuin-linked amino-activated silica beads [17].

References