Biomedical Engineering Reference
In-Depth Information
sialylated ligands are presented on this subunit (Diskin et al., 2009). Beside the β1-sunbunit
galectin-8 N-CRD also binds α5 and some other integrin-subunits, but literature does not
give a clear picture about the exact integrin binding partners. For example
N
-glycans on the
α4-subunit are once mentioned as main binding partner while other authors do not report
binding to this subunit. Similar discrepancies were noticed for other subunits (Cárcamo et
al., 2006; Diskin et al., 2009; Hadari et al., 2000; Nishi et al., 2003; Yamamoto et al., 2008).
This might be explained by tissue- or cell-specific glycosylation patterns of the single
subunits. In contrast to most interactions which are performed by the N-terminal galectin-8
CRD binding to the αM-subunit is performed by the C-terminal CRD (Nishi et al., 2003).
5. Galectin function in cell adhesion and cell migration
5.1 Principle function
Galectins can act pro- or antiadhesive for different cell types. They can either facilitate or
reduce adhesion to other cells depending on different factors. Cell adhesion is enhanced if
galectins crosslink glycosylated structures on one cell with glycans on other cells or the
extracellular matrix. In contrast the adhesion is reduced if soluble galectins block available
receptors for other binding interactions. This depends on one hand on galectin
concentration. At high concentrations galectins may block all available receptors without
interaction with each other which is necessary for crosslinking and therefore for adhesion
(Elola et al., 2007). It is for example discussed that galectin-3 outbursts can lead to
detachment of cells from the extracellular matrix as galectin-3 blocks integrin binding to
ECM glycoproteins (Ochieng et al., 1998b). On the other hand it is important which
receptors are available on the specific cell type used in the experiment and if those receptors
interact more easily with the soluble galectins or with receptors on the surface the cell
attaches to (Elola et al., 2007). Additional the oligomerisation state of the galectins plays an
important role as they can either block receptors or crosslink molecules depending on their
valency (Hughes, 2001). The oligomerisation is in case of galectin-1 depending on galectin
concentration while galectin-3 stays monomeric in solution without ligand binding and
builds pentamers after the binding reaction (Ahmad et al., 2004a; Cho & Cummings, 1995;
Cho & Cummings, 1997; Morris et al., 2004; Nieminen et al., 2008). Moreover effects of single
galectins can hardly be determined as most cell types co-express different galectins which
might at least partially result in overlapping or opposite effects (Cooper & Barondes, 1999;
Liu & Rabinovich, 2005).
In addition to direct binding of galectins to glycan structures on either membrane-bound
receptors or ECM-glycoproteins, regulation of integrin amount, availability and affinity by
galectin binding also contributes to adhesion events. Galectin-3 for example is able to
increase amount and/or affinity of β2-integrins on the cell surface on neutrophils, thereby
regulating the binding to ECM glycoproteins recognised by integrins (Hughes, 2001;
Kuwabara & Liu, 1996). Overexpression of galectin-3 correlates with enhanced surface
expression of α4β7 integrins resulting in increased cell adhesion (Matarrese et al., 2000). In
contrast binding of galectin-3 leads to internalisation of β1-integrins in breast carcinoma
cells (Furtak et al., 2001). Moreover the clustering and residence time of other receptors on
the cell surface is regulated by the formation of glycan-galectin lattices thereby regulating
different signalling processes (Garner & Baum, 2008; Lau & Dennis, 2008; Rabinovich et al.,
2007).
