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

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 (2021) Plasma Membrane Calcium ATPase-Neuroplastin Complexes Are Selectively Stabilized in GM1-Containing Lipid Rafts. International journal of molecular sciences, 22 (24). ISSN 1422-0067

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Official URL: https://www.mdpi.com/1422-0067/22/24/13590

Abstract

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.

Item Type:

Article

Uncontrolled Keywords:

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

Subjects:

BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences

Divisions:

Division of Physical Chemistry

Projects:

Project title	Project leader	Project code	Project type
Molekularni biljezi vulnerabilnosti, adaptacije i plastičnosti neurona u akutnoj i kroničnoj ozljedi mozga	Kalanj Bognar, Svjetlana	IP-2016-06-8636	HRZZ
Patofiziološke posljedice promjena sastava lipidnih splavi	UNSPECIFIED	IP-2014-09-2324	HRZZ
Eksperimentalna i klinička istraživanja hipoksijsko-ishemijskog oštećenja mozga u perinatalnoj i odrasloj dobi	Kostović, Ivica	KK.01.1.1.01.0007	EK