engleski

Submembrane distribution of neuroplastin and plasma membrane electrogenic pumps in mouse brain depends on ganglioside composition

Aim of this study was to investigate the effect of ganglioside composition on the distribution of electrogenic pumps, Na+/K+-ATPase (NKA) and plasma membrane Ca2+ ATPase (PMCA), and of synaptic glycoprotein neuroplastin (Np) across different membrane subdomains. Gangliosides, plasma membrane glycosphingolipids, are known to modulate localization and function of membrane proteins. Being particularly abundant in nervous tissue, they play an important role in signaling events affecting neural development and the pathogenesis of various diseases. Np is involved in cognition and memory formation, and being a PMCA auxiliary subunit also has an impact on intracellular Ca2+ homeostasis. We used St8sia1 null and B4galnt1 null mice with impaired synthesis of complex gangliosides. Wild type (WT) and null mice littermates of both mouse models were sacrificed and membrane fractions from the cortices were isolated by ultracentrifugation in discontinuous sucrose gradients. The localization of Np, NKA and PMCA was analyzed by Western blotting. Data revealed a different localization pattern of Np, NKA and PMCA across LR and nLR membrane subdomains. In each mouse model proteins have been observed in both LR and nLR fractions, whilst their localization in WT mice was more robust in the nLR subdomains. The results indicate a prominent shift for Np, NKA and PMCA between different membrane subdomains, depending on specific ganglioside composition. We propose that gangliosides may modulate the function of Np, NKA and PMCA, and thus contribute to maintenance of the ion homeostasis in nervous tissue.

lipid rafts ; glycosphingolipids ; PMCA ; sodium potassium ATPase

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