Chemistry Reference
In-Depth Information
21.2.2
Glycolipids
The organization of GSLs into microdomains on the cell surface and their role in
cellular recognition and adhesion is described in Chapter 10. Here, we focus on
the role of carbohydrate- carbohydrate interactions in such GSL - mediated phe-
nomena (for reviews, see [9, 10] and [1]; for synthesis and structures, see Chapters
10 and 30; for functional aspects of gangliosides, see Chapter 25).
21.2.2.1
L e
x
- L e
x
Interactions
It was far more diffi cult to determine specifi c carbohydrate - carbohydrate interac-
tions between glycoconjugates of proteoglycans or glycoproteins than of glyco-
lipids because, in the former case, the protein portion may have acted as a lectin.
Thus, specifi c carbohydrate-carbohydrate interaction was fi rst shown for glyco-
lipids (Le
x
- Le
x
) and only later for sponge proteoglycans (see Table 7.4 and Table
27.2 for structures). Embryonal stem cells and embryonal carcinoma cells express-
ing Le
x
at the cell surface, but not Le
x
-negative cells, have been shown to autoag-
gregate through a Ca
2+
- dependent interaction independent of E - cadherin [11] . The
autoaggregation mimics compaction of morula- stage mouse embryos - the fi rst
in a series of adhesion events during embryogenesis. E-cadherin is coexpressed
with Le
x
during compaction but the process proceeds well in an E- cadherin knock-
out mouse. These fi ndings suggest that embryonal compaction and cell autoag-
gregation depend on a cooperative effect of Le
x
- and E - cadherin - dependent
adhesion. It supports the notion that cell adhesion consists of multiple redundant
steps initiated by fl exible, reversible carbohydrate- carbohydrate recognition, fol-
lowed by reinforcing protein-carbohydrate and protein-protein interactions
(Figure 21.3 ).
Binding affi nity studies by SPR spectroscopy revealed that Le
x
trisaccharides
linked to self-assembled monolayers of alkanethiolate on gold fi lms strongly bound
soluble Le
x
trisaccharides (
K
d
= 5.4
1 0
− 7
M) [12] . The interaction force between
individual Le
x
molecules measured by AFM is 20 pN, one of the lowest biomolecu-
lar adhesion forces reported to date [10]. This example is consistent with the view
that weak binding forces between single molecules can become biologically
relevant due to the presence of large amounts of oligosaccharide chains on cell
surfaces and of multiple binding sites on each chain, assembling a powerful
recognition system based on versatile polyvalent interactions.
×
21.2.2.2
G b 4 - Dependent Adhesion
Autoaggregation of human embryonal carcinoma 2102 or TERA- 2 cells constitutes
a model of primate embryonic compaction process. Le
x
is highly down-regulated
on these cells, but they abundantly express lactoneotetraosylceramide (nLc
4
), glo-
boside (Gb4, see Table 10.2 for structures), and extended globo series GSLs termed
stage - specifi c embryonic antigen ( SSEA ) - 3 and -4 (for structures and further
details, see Chapter 10.6 and Table 24.3) that are maximally expressed at morula
stage and possibly mediate the compaction process of the primate (presumably
