Biology Reference
In-Depth Information
fragments and subsequent cellular uptake and complete degradation, without a
strict need for a particle-directed (phagocytic) uptake mechanism. However, even
in the case of a phagocytic uptake process, initial enzymatic cleavage steps are
likely to be required, considering the very large size of intact collagen fibers. In
accordance with this view, the
1 integrin-dependent phagocytosis of fibrillar
collagen by gingival fibroblasts was found to be increased after overexpression of
MMP-14 and decreased after MMP-14 downregulation (Lee et al.
2006
). Thus it
appears that, not unexpectedly, MMP-14 undertakes important steps of collagen
cleavage, even in this system.
b
1A
3A
1
5
4
2
3
Fig. 3.3
Cooperation between proteolysis and endocytosis in collagen turnover
. Collagen fibers,
being very large structures, are initially fragmented into large cleavage products before cellular
uptake or further degradation in the extracellular space. MT1-MMPs play a central role in this
initial fragmentation (1). Alternatively, this cleavage may be accomplished by soluble collage-
nases (1A). The resulting large products may be taken up by some cell types in a phagocytic
process, dependent on
b
1 integrins (2). Alternatively, further cleavage of the triple-helical
collagen is accomplished by MT-MMPs (3) or soluble collagenases (3A), in both cases resulting
in specific “1/4” and “3/4” fragments that gradually undergo denaturation and acquire a gelatin-
like state. The gelatin-like products are efficiently endocytosed by mannose receptor family
receptors such as Endo180/uPARAP (4), routed to lysosomes and degraded. Alternatively, further
degradation of the gelatin material may occur extracellularly, catalyzed by gelatinases (5) or other
proteases. Symbols depicting integrin and mannose receptor-type receptors and MMPs are the
same as in Figs.
3.1
and
3.2
.(
Black arrows
) proteolytic attack, (
red arrows
) cellular uptake.
Although in this figure all membrane proteins are depicted on a continuous “plasma membrane,”
this does not implicate that the active players must necessarily reside on the same cell
