The immunoglobulin‐superfamily molecule basigin is a binding protein for oligomannosidic carbohydrates: an anti‐idiotypic approach

Abstract

Recognition molecules that carry carbohydrate structures regulate cell interactions during development and play important roles in synaptic plasticity and regeneration in the adult. Glycans appear to be involved in these interactions. We have searched for binding proteins for oligomannosidic structures using the L3 antibody directed against high mannose-type glycans in an anti-idiotypic approach. A selected monoclonal anti-idiotype antibody was used for affinity chromatography and identified basigin as a binding protein from mouse brain detergent lysates. Basigin was found to bind to high mannose-carrying cell recognition molecules, such as myelin-associated glycoprotein, L1, the b2-subunit of Na + /K + -ATPase and an oligomannosidic neoglycolipid. Furthermore, basigin was involved in outgrowth of astrocytic processes in vitro. A striking homology between the first immunoglobulin (Ig)-like domain of basigin and the fourth Ig-like domain of NCAM, previously shown to bind to oligomannosidic glycans, and the lectin domain of the mannose receptor confirms that basigin is an oligomannose binding lectin. To our knowledge this is the first report that anti-idiotypic antibodies can be used to identify binding partners for carbohydrates. Keywords: anti-idiotypic antibody, basigin, cell recognition, lectin, nervous system, oligomannosidic glycans. Despite the overwhelming evidence that carbohydrates and their respective receptors are involved in cell recognition, direct evidence that oligosaccharides play important functional roles in the nervous system has remained relatively sparse. Indirect support for such a function has been derived from the temporally and spatially restricted pattern of expression of cell surface carbohydrates and their putative receptors (for reviews see: Schachner and Martini 1995;Rutishauser 1998;Lander and Selleck 2000). A functional involvement of carbohydrate structures in cell recognition has been demonstrated for the spatially and temporally regulated attachment of polysialic acid to neural cell adhesion molecule NCAM (for review see: Rutishauser 1998). Further examples for carbohydrate structures in the nervous system are the HNK-1, L3, L4 and L5 epitopes which are found on several neural recognition molecules. The L5 epitope, which is identical to the Lewis x -carbohydrate (Streit et al. 1996), is present on several neural recognition molecules and is involved in extension of astrocytic processes (Streit et al. 1993) and neural induction (Roberts et al. 1991). The HNK-1 carbohydrate structure containing an unusual 3¢-sulfated glucuronic acid (Chou

Mouse Na+/K+-ATPase β1-subunit has a K+-dependent cell adhesion activity for β-GlcNAc-terminating glycans

“…Furthermore, mannose but not lactose also strongly inhibited aggregate formation. This observation is probably due to the participation of high mannose-type oligosaccharides on the myelin-associated glycoprotein and L1 in neural cell adhesion by recognition with N-CAM and basigin (27,28), which is independent of the present ␤1-subunit-mediated cellular interaction.…”

“…Recently, this interaction has been shown to be mediated by the binding of N-CAM͞L1 molecules on neural cells to oligosaccharides expressed on the ␤2-subunit on glial cells (27). Furthermore, because the neonatal lethality of a ␤2-subunit gene deficiency in mice can be restored by the ␤1-subunit-knock-in method (21), the ␤1-subunit can take the place of the ␤2-subunit.…”

Synapsin I Is an Oligomannose-Carrying Glycoprotein, Acts As an Oligomannose-Binding Lectin, and Promotes Neurite Outgrowth and Neuronal Survival When Released via Glia-Derived Exosomes

“…Proteins that bind these oligomannoses as oligomannosebinding lectin-like proteins are the cell adhesion molecules NCAM and basigin (Horstkorte et al, 1993;Heller et al, 2003). Basigin, which is an important player in neuron-glia interactions and in the formation and/or maintenance of the blood-brain barrier, promotes outgrowth of astrocytic processes in an oligomannosedependent manner (Heller et al, 2003).…”

“…Basigin, which is an important player in neuron-glia interactions and in the formation and/or maintenance of the blood-brain barrier, promotes outgrowth of astrocytic processes in an oligomannosedependent manner (Heller et al, 2003). The interaction of NCAM with L1 depends on oligomannoses on L1, and disturbance of this oligomannose-dependent interaction reduces L1-induced neurite outgrowth (Horstkorte et al, 1993).…”

Synthetic emmprin peptides inhibit tumor cell-fibroblast interaction-stimulated upregulation of MMP-2 and tumor cell invasion

“…The third possible inhibitory mechanism could involve the lectin activity of emmprin (32). The fourth Ig-like domain of neural cell adhesion molecule (NCAM) is a lectin domain, and NCAM forms a complex with another neural adhesion molecule L1 via oligomannosidic carbohydrates on L1.…”