Pital (to H. J. J. and also a. P.). 1 To whom correspondence needs to be addressed: Finsen Laboratory, Rigshospitalet/BRIC, Copenhagen Biocenter, Ole Maaloesvej five, DK-2200, Copenhagen N, Denmark. Tel.: 45-35-45-60-31; Fax: 45-35-45-37-97; E-mail: [email protected] complex collagen structures of your extracellular matrix (ECM)2 undergo continuous remodeling during improvement and homeostasis of adult tissues. In pathological circumstances, the balance amongst collagen synthesis and turnover can be disrupted and this could result in excessive degradation or accumulation of collagen structures with severe consequences for the affected tissue(s). Osteoporosis, arthritis, fibrosis, and cancer represent such diseases (1, two). Elucidating mechanisms of collagen remodeling is hence of great value to fully comprehend and in the end cease the progression of these devastating illnesses. Two common pathways have already been described for the turnover of collagen: an extracellular pathway, governed by specific secreted or membrane-bound proteases, like Cathepsin K and members in the matrix metalloproteinase (MMP) loved ones, and an intracellular pathway, where partially fragmented collagen elements are transported to lysosomal compartments for proteolytic degradation (three?six). Unique cell surface receptors have already been suggested to facilitate internalization of collagens, like certain 1 integrins with phagocytic functions (7) and, importantly, the loved ones of endocytic receptors designated the mannose receptor (MR) household (for assessment see Ref. 8). Studies on one particular member in the MR household, the urokinase plasminogen activator receptor-associated protein (uPARAP, Endo180, MRC2, CD280, denoted uPARAP from right here on) (9 ?two), revealed the pivotal role from the intracellular collagen degradation pathway in biological and pathological processes.The abbreviations made use of are: ECM, extracellular matrix; MMP, matrix metalloproteinase; MR, mannose receptor; uPARAP, urokinase plasminogen activator receptor-associated protein; PLA2R, phospholipase A2 receptor; Cysrich, cysteine-rich; FN-II, fibronectin type-II; CTLD, C-type lectin-like domain; WGA, wheat germ agglutinin; PLA2, phospholipase A2; USER, uracil specific excision reagent; mAb, monoclonal antibody.Buy4-Methylbenzene-1,3-diol MARCH 14, 2014 ?VOLUME 289 ?NUMBERJOURNAL OF BIOLOGICAL CHEMISTRYMannose Receptor Family and Collagen EndocytosisuPARAP has therefore far been shown to be significant in bone improvement (13?5), protection against fibrosis in the liver, lungs, and kidneys (16 ?eight), and to market development and tissue destruction in cancer in mice (19, 20). uPARAP has also been shown to be up-regulated within a selection of human cancers (20 ?four), and not too long ago, a genome-wide association study recommended a link involving the MRC2 gene encoding uPARAP and temporomandibular joint osteoarthritis (25).1867923-49-6 structure The MR family members, in addition to uPARAP, consists of MR (MRC1, CD206), the phospholipase A2 receptor (PLA2R, PLA2R1), and DEC-205 (Ly75, CD205).PMID:23771862 All are constitutively recycling endocytic type-1 transmembrane proteins (26 ?2) and they include a hugely conserved domain composition, such as a cysteine-rich (Cys-rich) domain, a FN-II domain, as well as a variety of C-type lectin-like domains (CTLD), of which most, even so, possess no carbohydrate binding activity. The four members are all candidate collagen receptors, as recommended resulting from a typical putative collagen-binding area centered about the FN-II domain (8, 10, 30, 33?six). FN-II domains are well-characterized mediators of collagen.
