engleski

Neuroplastin in view of altered ganglioside environment

Gangliosides are sialic acid-bearing membrane glycosphingolipids especially abundant in mammalian central nervous system. Due to their ceramide moiety anchored in the plasma membrane and their carbohydrate portion protruding from the cell, gangliosides interact with molecules on adjacent cells and extracelullar matrix (trans interactions), as well as molecules within the same membrane (cis interactions). Additionally, gangliosides are not evenly distributed throughout the membrane, but rather more concentrated in organized microdomains lipid rafts. Disruption in membrane lipid composition causes specific raft proteins (e.g. neural cell adhesion molecule, NCAM) to disperse from lipid rafts which can have a significant impact on their function. Since specific ganglioside species fulfil particular roles in neuron-glia interactions, altered ganglioside composition would therefore have a profound effect on membrane proteins – either through direct binding, or simply by disrupting lipid rafts. In order to elucidate the effect of changed ganglioside environment on membrane proteins, we used genetically altered mouse models with deficient ganglioside synthesis in a screen for gene expression which may correlate with changes in ganglioside expression. Mice with a disrupted B4galnt1 gene (B4galnt1 null mice) lack the enzyme GM2/GD2 synthase and consequently do not synthesize the major gangliosides common to vertebrate brain but instead synthesize comparable amounts of simpler gangliosides. We detected several genes that are differentially expressed in B4galnt1 null mice compared to wild-type mice, including neuroplastin. Increased neuroplastin gene expression in hippocampus and cerebellum of B4galnt1 null mice was further confirmed by qRT-PCR. Additionally, Western blotting for hippocampus and cerebellum and immunohistochemical analysis of whole brain sections were performed. The most striking differences in immunoreactivity were observed in the hippocampus of B4galnt1 null mice compared to wild type mice. Specifically, B4galnt1 null mice had relatively low neuroplastin immunoreactivity in the pyramidal layer of CA1 and CA2 whereas wild type mice had strong neuroplastin staining of pyramidal cells. These findings strongly indicate that neuroplastin expression is perturbed as a consequence of changed ganglioside environment of neural membranes. As both neuroplastin and gangliosides have important roles in synaptic transmission, synaptic plasticity, and neurite outgrowth, these observations imply a potential interplay between gangliosides and neuroplastin which should be investigated further.

gangliosides; B4galnt1 null mice; neuroplastin

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