Plasma membrane calcium ATPase-neuroplastin complexes are selectively stabilized in GM1-containing lipid rafts

Katarina Ilic, Xiao Lin, Ayse Malci, Mario Stojanović, Borna Puljko, Marko Rožman, Željka Vukelić, Marija Heffer, Dirk Montag, Ronald L. Schnaar, Svjetlana Kalanj-Bognar, Rodrigo Herrera-Molina, Kristina Mlinac-Jerkovic

Research output: Contribution to journalArticlepeer-review


The recent identification of plasma membrane (Ca2+)-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.

Original languageEnglish (US)
Article number13590
JournalInternational journal of molecular sciences
Issue number24
StatePublished - Dec 1 2021


  • B4galnt1
  • GM2/GD2 synthase
  • Gangliosides
  • Glycosphingolipids
  • Membrane microdomains
  • Neuronal calcium homeostasis

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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