Plasma Membrane Calcium ATPase-Neuroplastin Complexes Are Selectively Stabilized in GM1-Containing Lipid Rafts.
Plasma Membrane Calcium ATPase-Neuroplastin Complexes Are Selectively Stabilized in GM1-Containing Lipid Rafts.
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DOI：
10.3390/ijms222413590
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发表时间：
2021-12-18
影响因子：
5.6
通讯作者：
Mlinac-Jerkovic K
中科院分区：
文献类型：
--
作者：
Ilic K;Lin X;Malci A;Stojanović M;Puljko B;Rožman M;Vukelić Ž;Heffer M;Montag D;Schnaar RL;Kalanj-Bognar S;Herrera-Molina R;Mlinac-Jerkovic K
最近发现的质膜（Ca 2+）-ATP酶（PMCA）-神经质蛋白（Np）复合物重新引起了对细胞溶质钙排出的细胞调节的关注，这在神经元中特别相关。在这里，我们测试的假设，PMCA-神经致活素复合物存在于特定的神经节苷脂含有筏，这可能会影响钙稳态。我们分析了所有四个PMCA旁系同源物（PMCA 1 -4）和神经质异构体（Np 65和Np 55）的脂筏和散装膜组分从GM 2/GD 2脱氢酶缺陷小鼠大脑的丰度。在这些组分中，我们发现Np 65/Np 55和选定的PMCA亚型（即PMCA 1和2）的分布改变。细胞表面染色和共聚焦显微镜鉴定GM 1作为主要的复合神经节苷脂共定位与神经致活蛋白在培养的海马神经元。此外，用特异性抗体阻断GM 1导致海马神经元索马中电诱发钙瞬变的钙恢复延迟。所有神经节苷脂种类的含量和组成在Neuroplastin缺陷小鼠脑中保持不变。因此，我们得出结论，改变的组合物或解体的神经节苷脂筏的结果在改变调节的钙信号在神经元中。我们建议，GM 1可能是一个关键的鞘脂，以确保适当的位置的PMCA-神经致活酶复合物进入筏，以参与调节神经元钙稳态。
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.
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影响因子：
5.5
作者：
Ilic, Katarina;Auer, Benedikt;Herrera-Molina, Rodrigo
通讯作者：
Herrera-Molina, Rodrigo
影响因子：
5.3
作者：
Chiavegatto, S;Sun, J;Schnaar, RL
通讯作者：
Schnaar, RL
影响因子：
4.8
作者：
Herrera-Molina, Rodrigo;Sarto-Jackson, Isabella;Montag, Dirk
通讯作者：
Montag, Dirk
DOI：
10.1016/j.bbrc.2016.07.117
发表时间：
2017-02-19
影响因子：
3.1
作者：
Brini, Marisa;Carafoli, Ernesto;Cali, Tito
通讯作者：
Cali, Tito
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影响因子：
16.6
作者：
Gong D;Chi X;Ren K;Huang G;Zhou G;Yan N;Lei J;Zhou Q
通讯作者：
Zhou Q