The C-type lectin receptor Endo180 displays internalization and recycling properties distinct from other members of the mannose receptor family.
Endo180/urokinase plasminogen activator receptor-associated protein together with the mannose receptor, the phospholipase A(2) receptor, and DEC-205/MR6-gp200 comprise the four members of the mannose receptor family. These receptors have a unique structural composition due to the presence of multiple C-type lectin-like domains within a single polypeptide backbone. In addition, they are all constitutively internalized from the plasma membrane via clathrin-mediated endocytosis and recycled back to the cell surface. Endo180 is a multifunctional receptor displaying Ca(2+)-dependent lectin activity, collagen binding, and association with the urokinase plasminogen activator receptor, and it has a proposed role in extracellular matrix degradation and remodeling. Within their short cytoplasmic domains, all four receptors contain both a conserved tyrosine-based and dihydrophobic-based putative endocytosis motif. Unexpectedly, Endo180 was found to be distinct within the family in that the tyrosine-based motif is not required for efficient delivery to and recycling from early endosomes. By contrast, receptor internalization is completely dependent on the dihydrophobic motif and modulated by a conserved upstream acidic residue. Furthermore, unlike the mannose receptor, Endo180 does not function as a phagocytic receptor in vitro. These findings demonstrate that despite an overall structural similarity, members of this receptor family employ distinct trafficking mechanisms that may reflect important differences in their physiological functions.
Howard
Matthew J
MJ
Breakthrough Toby Robins Breast Cancer Research Centre, Institute of Cancer Research, Mary-Jean Mitchell Green Building, Chester Beatty Laboratories, 237 Fulham Rd., London SW3 6JB, United Kingdom.
Isacke
Clare M
CM
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001859:Bone Neoplasms; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D006224:Cricetinae; D006801:Humans; D007700:Kinetics; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D012516:Osteosarcoma; D021381:Protein Transport; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000378:metabolism; D011975:Receptors, Mitogen / Q000235:genetics / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D011994:Recombinant Proteins / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured
C408294:Endo180; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D008562:Membrane Glycoproteins; C524898:PLAUR protein, human; C524899:Plaur protein, mouse; D011956:Receptors, Cell Surface; D011975:Receptors, Mitogen; D055293:Receptors, Urokinase Plasminogen Activator; D011994:Recombinant Proteins; D003094:Collagen; D002118:Calcium