title: A targeted deletion in the endocytic receptor gene Endo180 results in a defect in collagen uptake.
abstract: 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). In addition, all have a short cytoplasmic domain, which mediates their constitutive recycling between the plasma membrane and the endosomal apparatus, suggesting that these receptors function to internalize ligands for intracellular delivery. 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. Analysis of embryonic fibroblasts reveals that this mutation does not disrupt the C-type lectin activity that is mediated by CTLD2, but results in cells that have a defect in collagen binding and internalization and an impaired migratory phenotype.
authors.affiliation: The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK.
authors.forename: Lucy
authors.initials: L
authors.lastname: East
authors.forename: Afshan
authors.initials: A
authors.lastname: McCarthy
authors.forename: Dirk
authors.initials: D
authors.lastname: Wienke
authors.forename: Justin
authors.initials: J
authors.lastname: Sturge
authors.forename: Alan
authors.initials: A
authors.lastname: Ashworth
authors.forename: Clare M
authors.initials: CM
authors.lastname: Isacke
mesh_terms: D000818:Animals; D002465:Cell Movement; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D005347:Fibroblasts; D005786:Gene Expression Regulation; D037181:Lectins, C-Type / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D051379:Mice; D011485:Protein Binding; D021381:Protein Transport; D011975:Receptors, Mitogen / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D017384:Sequence Deletion / Q000235:genetics*
chemical_list: C408294:Endo180; D037181:Lectins, C-Type; D008024:Ligands; D011975:Receptors, Mitogen; D003094:Collagen