Cooperation Between Proteolysis and Endocytosis in Collagen Turnover - Extracellular Matrix Degradation - page 64

A different study, based on transplanted tumors, has addressed the function of
uPARAP-expressing tumor cells. After transfection of uPARAP/Endo180-negative
human MCF-7 cells with a uPARAP/Endo180 expression vector and injection
into immunocompromised mice, it could be shown that tumors formed by the
receptor-transfected cells grew more rapidly than mock-transfected cells (Wienke
et al. 2007 ).
3.3.1.2 Mannose Receptor
The MR (CD206) has a protein sequence and domain characteristics very similar to
those of uPARAP/Endo180, although the active carbohydrate-binding domain is, in
this case, the fourth of the eight lectin-like domains [reviewed in East and Isacke
( 2002 )], and the sequence elements in the cytoplasmic domains that govern endo-
cytosis of the two receptors are different (Howard and Isacke 2002 ; Schweizer et al.
2000 ). The MR has a fibronectin type II domain with a high sequence homology to
that of uPARAP/Endo180, and this domain is likely to be crucial for the collagen-
binding activity of MR (Napper et al. 2006 ). The present discussion of the activity
of MR will be limited to this type of interaction, although the major part of the
studies performed on this receptor to date has focused on the lectin activity, the
binding to pathogens, and additional roles in the immune system [reviewed in
Taylor et al. ( 2005 )].
In a purified system, the extracellular part of MR can bind to gelatin-agarose
(Napper et al. 2006 ), and Fc fusion proteins containing the N-terminal part (includ-
ing the fibronectin type II domain) of MR have been shown to bind to collagens of
several subtypes, and to denatured collagen (gelatin). Furthermore, in the latter
study it was shown that the endogenous MR on mouse bone marrow macrophages is
solely responsible for the ability of these cells to internalize gelatin and collagen
type IV because this ability was lost in macrophages from MR-deficient mice. MR
is widely expressed on macrophages but also occurs on hepatic (see below) and
lymphatic endothelial cells and in a few other cell types [reviewed in Taylor et al.
( 2005 )]. Evidence for the function of MR in collagen uptake in vivo is presented in
Sect. 3.4.2 .
3.3.1.3 A Function for PLA2R and DEC-205 in Collagen Internalization
For the last two protein family members, PLA2R and DEC-205, very little is known
about any roles in collagen endocytosis. The two receptors are mentioned here,
mostly because they show a pronounced structural similarity (including their fibronec-
tin type-II domains) with uPARAP/Endo180 and MR [reviewed in East and Isacke
( 2002 )]. An early finding with PLA2R, however, was indeed a collagen interaction
directed to its fibronectin type-II domain (Ancian et al. 1995 ). PLA2R-deficient