Glycosphingolipids within membrane contact sites influence their function as signaling hubs in neurodegenerative diseases.
Glycosphingolipids within membrane contact sites influence their function as signaling hubs in neurodegenerative diseases.
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DOI：
10.1002/2211-5463.13605
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发表时间：
2023-09
期刊：
影响因子：
2.6
通讯作者：
d'Azzo, Alessandra
中科院分区：
文献类型：
--
作者：
Weesner, Jason Andrew;Annunziata, Ida;van de Vlekkert, Diantha;d'Azzo, Alessandra
细胞内细胞器通过专门的膜接触位点（MCS）进行广泛的细胞器间通信来执行它们的许多功能，其中两个细胞器彼此拴系或与质膜（PM）拴系而不融合。近年来，这些普遍存在的膜结构已经成为控制多种细胞途径的中央信号枢纽，从脂质代谢/转运到代谢物和离子的交换（即，Ca 2+）和一般细胞器生物发生。在MCSs的并列膜之间的功能串扰依赖于一个定义的复合蛋白质和脂质，填充这些微区在一个动态的方式。这在神经系统中特别重要，其中已显示MCS组成的改变影响其功能，并与神经退行性疾病的发病机制有关。在这篇综述中，我们重点介绍了由内质网（ER）与线粒体、内质网与内溶酶体以及线粒体与溶酶体拴系形成的MCS。我们强调了鞘糖脂是如何异常处理/降解和异位积累在细胞内膜和PM改变MCS的拓扑结构，破坏信号通路，导致神经元死亡和神经变性。特别是，我们专注于神经退行性溶酶体贮积病与改变鞘糖脂catalase。本文综述了鞘糖脂（GSL），聚集在特定的膜接触位点（MCS），对它们的蛋白质和脂质的组成和功能的影响。由于其异常的catalysts导致的MCS中GSL水平的改变影响其结构特征和信号传导特性，导致溶酶体贮积病中的神经变性：戈谢病、GM 1-神经节苷脂沉积症和尼曼-匹克C型。
Intracellular organelles carry out many of their functions by engaging in extensive interorganellar communication through specialized membrane contact sites (MCSs) formed where two organelles tether to each other or to the plasma membrane (PM) without fusing. In recent years, these ubiquitous membrane structures have emerged as central signaling hubs that control a multitude of cellular pathways, ranging from lipid metabolism/transport to the exchange of metabolites and ions (i.e., Ca2+), and general organellar biogenesis. The functional crosstalk between juxtaposed membranes at MCSs relies on a defined composite of proteins and lipids that populate these microdomains in a dynamic fashion. This is particularly important in the nervous system, where alterations in the composition of MCSs have been shown to affect their functions and have been implicated in the pathogenesis of neurodegenerative diseases. In this review, we focus on the MCSs that are formed by the tethering of the endoplasmic reticulum (ER) to the mitochondria, the ER to the endo‐lysosomes and the mitochondria to the lysosomes. We highlight how glycosphingolipids that are aberrantly processed/degraded and accumulate ectopically in intracellular membranes and the PM change the topology of MCSs, disrupting signaling pathways that lead to neuronal demise and neurodegeneration. In particular, we focus on neurodegenerative lysosomal storage diseases linked to altered glycosphingolipid catabolism. This review focuses on the impact of glycosphingolipids (GSLs), clustered within specific membrane contact sites (MCSs), on their protein and lipid compositions and function. Alterations in GSL levels at MCSs due to their abnormal catabolism affect their structural characteristics and signaling properties, leading to neurodegeneration in the lysosomal storage diseases: Gaucher disease, GM1‐gangliosidosis and Niemann‐Pick Type C.
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影响因子：
15.9
作者：
Cisneros J;Belton TB;Shum GC;Molakal CG;Wong YC
通讯作者：
Wong YC
影响因子：
3.5
作者：
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通讯作者：
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DOI：
10.1016/j.bbalip.2016.01.020
发表时间：
2016-08
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
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通讯作者：
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影响因子：
4.6
作者：
Aston D;Capel RA;Ford KL;Christian HC;Mirams GR;Rog-Zielinska EA;Kohl P;Galione A;Burton RA;Terrar DA
通讯作者：
Terrar DA
DOI：
10.1126/science.aab1370
发表时间：
2015-07-24
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
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通讯作者：
De Camilli P