Carbohydrate-independent recognition of collagens by the macrophage mannose receptor.
Mannose receptor (MR) is the best characterised member of a family of four endocytic molecules that share a common domain structure; a cysteine-rich (CR) domain, a fibronectin-type II (FNII) domain and tandemly arranged C-type lectin-like domains (CTLD, eight in the case of MR). Two distinct lectin activities have been described for MR. The CR domain recognises sulphated carbohydrates while the CTLD mediate binding to mannose, fucose or N-acetylglucosamine. FNII domains are known to be important for collagen binding and this has been studied in the context of two members of the MR family, Endo180 and the phospholipase A2 receptor. Here, we have investigated whether the broad and effective lectin activity mediated by the CR domain and CTLD of MR is favoured to the detriment of FNII-mediated interaction(s). We show that MR is able to bind and internalise collagen in a carbohydrate-independent manner and that MR deficient macrophages have a marked defect in collagen IV and gelatin internalisation. These data have major implications at the molecular level as there are now three distinct ligand-binding sites described for MR. Furthermore our findings extend the range of endogenous ligands recognised by MR, a molecule firmly placed at the interface between homeostasis and immunity.
Martinez-Pomares
Luisa
L
Sir William Dunn School of Pathology, Oxford, UK. luisa.martinez-pomares@nottingham.ac.uk
Wienke
Dirk
D
Stillion
Richard
R
McKenzie
Emma J
EJ
Arnold
James N
JN
Harris
James
J
McGreal
Eamon
E
Sim
Robert B
RB
Isacke
Clare M
CM
Gordon
Siamon
S
D000818:Animals; D001665:Binding Sites; D002241:Carbohydrates / Q000502:physiology*; D003094:Collagen / Q000737:chemistry / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D005780:Gelatin / Q000378:metabolism; D037181:Lectins, C-Type / Q000737:chemistry / Q000502:physiology*; D008264:Macrophages / Q000502:physiology*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000737:chemistry / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000502:physiology*
D002241:Carbohydrates; D005353:Fibronectins; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D005780:Gelatin; D003094:Collagen