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

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

Izvornik
International journal of molecular sciences (1422-0067) 22 (2021), 24; 13590, 17

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
neuronal calcium homeostasis ; gangliosides ; glycosphingolipids ; GM2/GD2 synthase ; B4galnt1 ; membrane microdomains

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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