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Plasma Membrane Calcium ATPase-Neuroplastin Complexes Are Selectively Stabilized in GM1-Containing Lipid Rafts. | LitMetric

AI Article Synopsis

  • Researchers found significant complexes form between plasma membrane calcium ATPase (PMCA) and Neuroplastin (Np) that play a role in regulating calcium levels, particularly in neurons.
  • They discovered that in mouse brains lacking certain gangliosides, the distribution of Neuroplastin and specific PMCA isoforms changed, suggesting that these proteins are part of lipid rafts.
  • Blocking GM1, a critical ganglioside, impaired calcium recovery in neurons, indicating that GM1 is essential for proper placement of PMCA-Neuroplastin complexes, which help maintain calcium balance in nerve cells.

Article Abstract

The recent identification of plasma membrane (Ca)-ATPase (PMCA)-Neuroplastin (Np) complexes has renewed attention on cell regulation of cytosolic calcium extrusion, which is of particular relevance in neurons. Here, we tested the hypothesis that PMCA-Neuroplastin complexes exist in specific ganglioside-containing rafts, which could affect calcium homeostasis. We analyzed the abundance of all four PMCA paralogs (PMCA1-4) and Neuroplastin isoforms (Np65 and Np55) in lipid rafts and bulk membrane fractions from GM2/GD2 synthase-deficient mouse brains. In these fractions, we found altered distribution of Np65/Np55 and selected PMCA isoforms, namely PMCA1 and 2. Cell surface staining and confocal microscopy identified GM1 as the main complex ganglioside co-localizing with Neuroplastin in cultured hippocampal neurons. Furthermore, blocking GM1 with a specific antibody resulted in delayed calcium restoration of electrically evoked calcium transients in the soma of hippocampal neurons. The content and composition of all ganglioside species were unchanged in Neuroplastin-deficient mouse brains. Therefore, we conclude that altered composition or disorganization of ganglioside-containing rafts results in changed regulation of calcium signals in neurons. We propose that GM1 could be a key sphingolipid for ensuring proper location of the PMCA-Neuroplastin complexes into rafts in order to participate in the regulation of neuronal calcium homeostasis.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8708829PMC
http://dx.doi.org/10.3390/ijms222413590DOI Listing

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