Biomedical Engineering Reference
In-Depth Information
4. Glycoproteins as binding partners of galectins
Galectins can act intracellular or in the extracellular space, where they have different
functions regulated by protein-protein or protein-glycan interactions. In the extracellular
space they interact with different glycoproteins influencing cell adhesion, signalling and
proliferation events. Thereby they interact with ECM-glycoproteins forming the
extracellular matrix and with glycosylated transmembrane or membrane associated proteins
on the cell surface (table 2). Following we present some selected binding partners of the
three different galectins discussed so far.
4.1 ECM glycoproteins as binding partners of galectins
Different extracellular matrix proteins contribute to structural and functional aspects of the
extracellular space. Galectin-1 interacts strongly with different extracellular matrix proteins.
It has affinity to several glycoproteins as with increasing affinity osteopontin, vitronectin,
thrombospondin, cellular fibronectin and laminin (Moiseeva et al., 2003). Most of these
interactions depend on the carbohydrate recognition domain and can be inhibited with
soluble glycan ligands (Cooper, 1997; Moiseeva et al., 2003; Ozeki et al., 1995; Zhou &
Cummings, 1993). Galectin-3 also shows high affinity for some ECM-glycoproteins (Dumic
et al., 2006; Kuwabara & Liu, 1996; Massa et al., 1993; Matarrese et al., 2000; Ochieng et al.,
1998b; Sato & Hughes, 1992). The best binding candidates fibronectin and laminin are
heavily glycosylated (5-7% and at least 12-15% respectively), carrying mainly
N
-glycans
(Paul & Hynes, 1984; Tanzer et al., 1993).
N
-glycans are among the main binding partners of
galectin-1, -3 and -8 (Patnaik et al., 2006) (although galectin-8 also shows high affinity to
some glycosphingolipids (Ideo et al., 2003; Yamamoto et al., 2008)). One third of laminin
N
-
glycans is composed of repetitive
“N
-acetyllactosamine” units (shown for mouse EHS-
laminin) which are preferentially recognised by galectin-3 but also by galectin-1 and to less
extent galectin-8 (Arumugham et al., 1986; Hirabayashi et al., 2002; Knibbs et al., 1989; Sato
& Hughes, 1992; Zhou & Cummings, 1993). The other ECM-glycoproteins carry also
N
-
glycans but are less glycosylated (Bunkenborg et al., 2004; Chen et al., 2009; Liu et al., 2005).
For example osteopontin from human bone shows only two
N
-glycans with binding sites
which are partially blocked by α6-bound sialic acid (Ideo et al., 2003; Masuda et al., 2000;
Stowell et al., 2008a). Another extracellular matrix protein interacting with galectin-1 and -3
is the Mac-2 binding protein or 90K antigen which influences adhesion processes (Sasaki et
al., 1998; Tinari et al., 2001).
The different ECM-proteins which are bound by galectins can interact with other ECM-
glycoproteins and/or integrins (Adams, 2001; Janik et al., 2010; Kariya et al., 2008; Singh et
al., 2010). These interactions can lead to regulatory effects, lattice formation and signalling
cascades.
4.2 Cell-surface glycoproteins as binding partners of galectins
Beside these soluble ECM components also some membrane-bound proteins are recognised
by galectins. One of these is the lysosome associated membrane glycoprotein 1 (LAMP-1)
which is known to carry several
N
-glycans partly presenting poly-lactosamine glycans
recognised by galectin-3 and -1 (Chen et al., 2009; Do et al., 1990; Dong & Hughes, 1997).
LAMP-1 is also known as CD107a. Several other membrane proteins associated in the
cluster of differentiation such as CD3, 4, 7, 8, 43 and 45 which are presented on T-cells are
