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

Scientific paper - Original scientific paper

• Author: Katarina Ilić
• Author: Xiao Lin
• Author: Ayse Malci
• Author: Mario Stojanović
• Author: Borna Puljko
• Author: Marko Rožman
• Author: Željka Vukelić
• Author: Marija Heffer
• Author: Dirk Montag
• Author: Ronald L. Schnaar
• Author: Svjetlana Kalanj-Bognar
• Author: Rodrigo Herrera-Molina
• Author: Kristina Mlinac-Jerković
• Author's institution: University of Zagreb; School of Medicine; (Department of Medical Chemistry, Biochemistry and Clinical Chemistry)
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences

Abstract (english)

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.

• Keywords (english): Animals; Brain / metabolism; Cells, Cultured; G(M1) Ganglioside / analysis; G(M1) Ganglioside / metabolism*; Male; Membrane Glycoproteins / analysis; Membrane Glycoproteins / metabolism*; Membrane Microdomains / metabolism*; Mice; Mice, Inbred C57BL; Neurons / metabolism; Plasma Membrane Calcium-Transporting ATPases / analysis; Plasma Membrane Calcium-Transporting ATPases / metabolism*
• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review
• Publication version: Published version
• Journal title: International Journal of Molecular Sciences
• Numbering: vol. 22, no. 24, 13590
• e-ISSN: 1422-0067
• DOI: https://doi.org/10.3390/ijms222413590
• URN:NBN: urn:nbn:hr:105:896617
• Publication: 2021-12-18
• Project: Number: IP-2016-06-8636; Title (croatian): Molekularni biljezi vulnerabilnosti, adaptacije i plastičnosti neurona u akutnoj i kroničnoj ozljedi mozga; Acronym: NeuroReact; Leader: Svjetlana Kalanj-Bognar; Jurisdiction: Croatia; Funding stream: IP
• Project: Number: IP-2014-09-2324; Title (croatian): Patofiziološke posljedice promjena sastava lipidnih splavi; Title (english): Pathophysiological consequences of lipid raft changes; Acronym: RafTuning; Jurisdiction: Croatia; Funding stream: IP
• Document URL: https://www.mdpi.com/1422-0067/22/24/13590
• Type of resource: Text
• Access conditions: Open access
• Created on: 2022-02-01 09:24:09