engleski

Effects of altered ganglioside environment on the expression and localization of selected membrane proteins in mammalian nervous tissue

Gangliosides are complex membrane glycosphingolipids with a plethora of roles in mammalian nervous system. Mice knockout models with disrupted ganglioside biosynthesis have been studied extensively ; still their phenotypes as well as all the full effects of altered ganglioside environment on various cellular processes have not been completely elucidated. The long-standing aim of our group is to unravel the network of membrane proteins as well as lipids affected by changes in ganglioside composition. For that purpose we used two mice knockout models with disrupted ganglioside biosynthesis. After initial gene expression profiling of brain tissue of knockout and wild-type mice using whole genome microarrays and bioinformatic analysis, we performed qRT-PCR, Western blotting and immunohistochemistry for several protein candidates. We focused our investigation on neuroplastin and sodium-potassium pump, and showed that there is a significant change in the transcriptomic and proteomic expression as well as the localisation of selected membrane proteins or some of their isoforms in brain tissue of mice with altered ganglioside biosynthesis. The distribution of neuroplastin, a cell adhesion molecule involved in synaptic plasticity and long-term potentiation, is markedly different in the hippocampus of mice with altered ganglioside synthesis. On the other hand, the disturbed function of sodium-potassium pump leads to altered nerve conductance and may explain seizure susceptibility in analyzed mice models. The exact intermolecular interactions between protein and glycolipid membrane constituents should be investigated further in order to elucidate the nature of their interplay in both physiological and pathological conditions, particularly during neurodevelopment, neurodegeneration and tumorigenesis.

Gangliosides; membrane proteins; neuroplastin

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