Biomedical Engineering Reference
In-Depth Information
2.3 Other specific features of galectins
2.3.1 Secretion
Different tissues are known to produce galectins and most of them secrete parts of the
cytosolic galectin pool. The amount of secreted galectin depends on cell type, differentiation
status and can be regulated by external triggers (Cooper, 2002; Hughes, 1999). Examples of
galectin producing cells with relevance for regenerative medicine are beside others neurons,
epithelial cells of several tissues and liver cells, which produce either several different
galectins or a specific subset of galectins (Dumic et al., 2006; Hughes, 1999).
Galectins act intra- and extracellularly. As known so far they are secreted via a non-classical
mechanism which is not fully understood yet. They lack classical signalling sequences for
specific localisation but can be found in the outer cellular space as well as inside the cells
even located in the nucleus (Hughes, 1999). Although the complex regulation of secretion
remains still elusive some explanations have been found: Galectin-1 secretion depends on
the binding to a counter-receptor molecule and does not involve plasma membrane
blebbing (Seelenmeyer et al., 2005; Seelenmeyer et al., 2008). Galectin-3 secretion seems also
to be regulated by binding to other proteins such as chaperons and subsequent vesicular
secretion (Hughes, 1999; Mehul & Hughes, 1997). The N-terminal-domain of galectin-3 is
important for subcellular translocation and secretion of the protein (Gong et al., 1999).
2.3.2 Galectin-1: Importance of reducing conditions
The lectin activity of galectin-1 depends on reduced cysteine residues. Oxidised galectin-1
has no lectin activity but functions in the regeneration of nerve axons (Horie et al., 2004).
Galectin-1 has six cysteine residues which are accessible to the solvent (see Fig. 2). The
removal of the most accessible cysteine (Cys2) (Lopez-Lucendo et al., 2004) - or better all
cysteine residues - enhances protein stability under both reducing and non-reducing
conditions significantly (Cho & Cummings, 1995; Nishi et al., 2008), while none of them is
necessary for lactose binding as shown by site directed mutagenesis and x-ray
crystallography (Hirabayashi & Kasai, 1991; Lopez-Lucendo et al., 2004).
2.3.3 Galectin-3: The only known chimera type galectin
Galectin-3 has some specific properties due to its unique structure. Galectin-3 consists of
three parts: 1) a N-terminal 12 amino acid leader sequence containing two phosphorylation
sites, 2) a proline and glycine rich collagen like domain necessary for oligomerisation and
3) the carbohydrate recognition domain (Ahmad et al., 2004a; Dumic et al., 2006; Kubler et
al., 2008; Mehul & Hughes, 1997; Nieminen et al., 2008). The first few amino acids forming
the leader peptide are important for the subcellular localisation and secretion of the protein
(Gong et al., 1999). Moreover phosphorylation of Ser6 seems to regulate affinity for different
ligands and thereby cellular activity of galectin-3 (Dumic et al., 2006; Mazurek et al., 2000;
Szabo et al., 2009; Yoshii et al., 2002). Galectin-3 can be cleaved by different proteases such
as metalloproteinases-2 and -9 (gelatinases A and B respectively), metalloproteinase-13
(collagenase-3) and with low activity metalloproteinase-1 (collagenase-1) separating the full-
length CRD from the N-terminal extension (Guévremont et al., 2004; Ochieng et al., 1994).
The main cleavage position is located between Ala62 and Tyr63 while other cleaving sites
are only recognised by some specific proteases to lesser extend (Dumic et al., 2006;
