what-when-how
In Depth Tutorials and Information
Cell
Extracellular Matrix
Hyalectans
Nucleus
Brovican
Glypican
Versican
NH
2
Neurocan
Aggrecan
NH
2
Serglycin
NH
2
NH
2
COOH
Syndecan
COOH
SLRP
COOH
Non-hyaluronan-binding PGs
COOH
Collagen XV
Collagen XVIII
Argin, Perfecan
Basement membrane
FIGURE 8.1
Classification of proteoglycans (PGs) based on their location and binding. The heterogeneous group of PGs includes those
of the extracellular matrix, such as small leucine-rich PGs (
SLRP
; e.g., decorin) and modular PGs. Modular PGs are divided into hyalec-
tans (hyaluronan- and lectin-binding PGs) and the non-hyaluronan-binding PGs of the basement membrane. The third group of cell-surface
PGs encompasses mainly the membrane-spanning syndecans (e.g., syndecan-4) and the glycosylphosphatidylinositol-anchored glypicans
(glypican-1). Serglycin is an intracellular PG found in hematopoietic and endothelial cells.
(Reproduced with permission from
12
.)
subtypes result in enormous diversity and provide the
structural basis for a multitude of biological functions.
The post-translational modifications, such as modifica-
tion in the degree and localization of sulfate groups and
glucoronic acid epimerization, further increase their
structural complexity. Post-translational modifications
of PGs can serve as an indicator for chronological age.
Interestingly, osteoblasts derived from OI patients of any
age had a “fetal-like” PG fingerprint with regard to PG
distribution, GAG maturity and
O-
linked modifications.
Moreover, increasing severity of OI was associated with
increasing
O-
linked oligosaccharide modifications.19
19
bound PG) or secreted into the pericellular environment
by secretory vesicles (i.e., SLRPs).
7,11
Based on their structure and localization PGs are
divided into three major categories:
1.
Small leucine-rich PGs (SLRPs)
2.
Modular PGs
3.
Cell surface PGs
A diagram depicting these classes and their cell ori-
entation is shown in
Figure 8.1
.
12
PGs are mostly found extracellularly or bound to
cellular membranes, thus, they have structural impor-
tance such as the control of collagen fibrillogenesis, as
well as regulatory properties. By binding a multitude
of cell surface receptors, cytokines and growth factors
(e.g., FGFs, VEGF, TGF-βs)
13-16
they are able to acti-
vate and modulate many signaling cascades and intra-
cellular pathways. In addition, they act both as a local
tissue-bound reservoir of growth factors and mediators
of morphogen gradient formation. As a result, they can
influence not only the cells themselves (i.e., prolifera-
tion, differentiation, adhesion and migration), but also
the composition of the matrix.
17,18
The combinations of different core proteins as well as
specific additions of at least one GAG chain of various
SLRPS
SLRPs are the most abundant PGs found in the bone
mineralized matrix. In addition to being structural pro-
teins, SLRPs constitute a network for signal regulation.
SLRPs affect intracellular phosphorylation,
20,21
a major
conduit of information for cellular responses; they mod-
ulate distinct pathways and control cell proliferation
and differentiation in a cell-specific fashion.
22,23
The core protein of the SLRP family members is
relatively small (36-42 kD). It is characterized by a
