{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMRC2 (also known as Endo180 or uPARAP) is a multifunctional, endocytic receptor of the macrophage mannose receptor family that plays a central role in extracellular matrix homeostasis. It binds native, denatured, and glycosylated collagens via its fibronectin type II domain and an active C‐type lectin domain, thereby mediating collagen internalization and lysosomal degradation. This activity not only facilitates normal connective tissue turnover but also contributes to the regulation of cell adhesion, cytoskeletal reorganization, and, in some contexts, even pathogen interactions such as macrophage‐mediated HIV binding and transmission."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn neoplastic settings, MRC2 expression is frequently upregulated and has been closely linked with increased tumor cell invasiveness and poor clinical outcomes. For example, in glioblastoma multiforme"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "and basal‐like breast cancers, elevated Endo180 levels promote the internalization and remodeling of collagen matrices, thereby enhancing cell motility and invasion. Its activity—by facilitating collagen uptake, modulating MT1‐MMP activation, and promoting actin cytoskeletal rearrangements—contributes to chemotactic responses and the degradation of extracellular matrix barriers in diverse malignancies such as head and neck squamous cell carcinoma"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ", prostate cancer"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "and"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ", gliomas"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ", and osteosarcoma."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " These functions are further underscored by studies showing that MRC2-driven collagen processing and alteration of the extracellular matrix architecture are associated with enhanced cell migration"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "and adverse prognosis in patient cohorts."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "15", "end_ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in cancer, MRC2 is distinguished by unique trafficking and signaling properties that set it apart from other members of the receptor family. Its endocytic routing relies on specific dihydrophobic motifs rather than conventional tyrosine‐based signals"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": ", and extrinsic factors—including surfactant protein A"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "20"}]}, {"type": "t", "text": "and advanced glycation end‐products—can modulate its function, influencing processes such as fibroblast-mediated immune regulation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "21"}]}, {"type": "t", "text": "and the pathogenesis of diabetic nephropathy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "22"}]}, {"type": "t", "text": " Although in some cell types Endo180 does not interact with certain substrates such as procollagenase 3"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "23"}]}, {"type": "t", "text": ", structural and biochemical studies have elucidated key aspects of its conformational flexibility and ligand binding"}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "24", "end_ref": "27"}]}, {"type": "t", "text": ", while its dysregulation is also linked to remodeling of the dermal matrix in photoaged skin."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "28"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Deborah Greene Nguyen, James E K Hildreth "}, {"type": "b", "children": [{"type": "t", "text": "Involvement of macrophage mannose receptor in the binding and transmission of HIV by macrophages."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Immunol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/immu.200310024"}], "href": "https://doi.org/10.1002/immu.200310024"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12645947"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12645947"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Lars H Engelholm, Karin List, Sarah Netzel-Arnett, et al. 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