engleski

Protein-lipid interplay in the neuronal membrane: gangliosides and specific glycoproteins as new interacting partners

Alterations in membrane organization have been reported in many human diseases. Hence, increasingly more attention is being drawn to the study of cell membrane dynamics with emphasis on exact interactions between individual protein and lipid membrane constituents. The long-standing objective of our group is to unravel the interplay between specific membrane glycoproteins and gangliosides, and to clarify its impact on (patho)physiological events in mammalian brain. For that purpose, we analyzed brain tissue of several genetically altered mouse models with disrupted ganglioside biosynthesis and consequent changed ganglioside composition. We employed whole genome expression analysis, qRT-PCR, Western blotting, immunohistochemistry, membrane subfractionation and high performance thin layer chromatography (HPTLC). We focused on several protein candidates with changed expression and/or localization. The most striking results obtained in our extensive study concern a cell-adhesion molecule neuroplastin implicated in various processes including synaptic plasticity and balancing the ratio of excitatory/inhibitory synapses. We observed changed total neuroplastin expression and a change in specific cell type distribution of neuroplastin in hippocampi of investigated mouse models. Furthermore, redistribution was prominent on a more elaborate scale: there is a shift of neuroplastin to different submembrane domains when membrane ganglioside composition is changed. The results clearly show that depending on specific ganglioside membrane milieu, there is an obvious and pronounced change in neuroplastin micro- and macro-distribution. Further experiments should elucidate the detailed nature of interactions between gangliosides and neuroplastin, which will contribute to the understanding of fundamental processes in nervous tissue in which gangliosides and neuroplastin have a role in.

neuroplastin ; gangliosides ; GM1 ; lipid rafts ; membrane proteins

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