Identification and characterization of the endocytic transmembrane glycoprotein Endo180 as a novel collagen receptor.
Endo180, a member of the mannose receptor family, is constitutively recycled between clathrin-coated pits on the cell surface and intracellular endosomes. Its large extracellular domain contains an N-terminal cysteine-rich domain, a single fibronectin type II domain and eight C-type lectin-like domains. The second of these lectin-like domains has been shown to mediate Ca2+-dependent mannose binding. In addition, cross-linking studies have identified Endo180 as a urokinase plasminogen activator receptor-associated protein and this interaction can be blocked by collagen V. Here we demonstrate directly using in vitro assays, cell-based studies and tissue immunohistochemistry that Endo180 binds both to native and denatured collagens and provide evidence that this is mediated by the fibronectin type II domain. In cell culture systems, expression of Endo180 results in the rapid uptake of soluble collagens for delivery to lysosomal degradative compartments. Together with the observed restricted expression of Endo180 in both embryonic and adult tissue, we propose that Endo180 plays a physiological role in mediating collagen matrix remodelling during tissue development and homeostasis and that the observed receptor upregulation in pathological conditions may contribute to disease progression.
Wienke
Dirk
D
The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, Chester Beatty Laboratories, London SW3 6JB, United Kingdom.
MacFadyen
John R
JR
Isacke
Clare M
CM
D000818:Animals; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004705:Endocytosis / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism* / Q000502:physiology; D005434:Flow Cytometry; D006801:Humans; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000502:physiology; D038981:Receptors, Collagen / Q000378:metabolism*; D011975:Receptors, Mitogen / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D020539:Sequence Analysis, Protein
C408294:Endo180; D038981:Receptors, Collagen; D011975:Receptors, Mitogen