16pdel lipid changes in iPSC-derived neurons and function of FAM57B in lipid metabolism and synaptogenesis.
16pdel lipid changes in iPSC-derived neurons and function of FAM57B in lipid metabolism and synaptogenesis.
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DOI：
10.1016/j.isci.2021.103551
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发表时间：
2022-01-21
期刊：
影响因子：
5.8
通讯作者：
Sive H
中科院分区：
文献类型：
--
作者：
Tomasello DL;Kim JL;Khodour Y;McCammon JM;Mitalipova M;Jaenisch R;Futerman AH;Sive H
复杂的16p11.2缺失综合征（16 pdel）伴有神经系统疾病，包括癫痫，自闭症谱系障碍和智力残疾。我们证明了来自受影响的人的16 pdel iPSC分化的神经元相对于未受影响的人显示出增强的局部场电位活性和改变的神经酰胺相关脂质种类。FAM 57 B是16 p11.2区间的一个特征较差的基因，已成为与症状相关的候选基因。我们发现，FAM 57 B调节神经酰胺合酶（CerS）的活性，但不是CerS本身。在FAM 57 B突变的人神经元细胞和斑马鱼脑中，与细胞膜相关的鞘脂和甘油脂的组成和水平被破坏。因此，我们观察到异常的质膜结构和突触蛋白的错误定位，这是伴随着抑郁的大脑和行为活动。总之，这些结果表明，FAM 57 B的单倍不足通过该基因在脂质代谢中的关键作用而导致16 pdel综合征中神经元活性和功能的变化。16 pdel神经元中LFP活性增强和性别特异性差异16 pdel神经元脂质组表明改变的神经酰胺相关物质FAM 57 B是脑中脂质调节所必需的神经酰胺合酶调节剂FAM 57 B在突触发生、突触结构和组成中的功能细胞神经科学;发育神经科学;分子神经科学;神经科学
The complex 16p11.2 deletion syndrome (16pdel) is accompanied by neurological disorders, including epilepsy, autism spectrum disorder, and intellectual disability. We demonstrated that 16pdel iPSC differentiated neurons from affected people show augmented local field potential activity and altered ceramide-related lipid species relative to unaffected. FAM57B, a poorly characterized gene in the 16p11.2 interval, has emerged as a candidate tied to symptomatology. We found that FAM57B modulates ceramide synthase (CerS) activity, but is not a CerS per se. In FAM57B mutant human neuronal cells and zebrafish brain, composition and levels of sphingolipids and glycerolipids associated with cellular membranes are disrupted. Consistently, we observed aberrant plasma membrane architecture and synaptic protein mislocalization, which were accompanied by depressed brain and behavioral activity. Together, these results suggest that haploinsufficiency of FAM57B contributes to changes in neuronal activity and function in 16pdel syndrome through a crucial role for the gene in lipid metabolism. Augmented LFP activity and sex-specific differences in 16pdel neurons 16pdel neuronal lipidome indicated altered ceramide related species FAM57B is a ceramide synthase modulator essential for lipid regulation in the brain FAM57B functions in synaptogenesis, synapse architecture, and composition Cellular neuroscience; Developmental neuroscience; Molecular neuroscience; Neuroscience
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影响因子：
7.4
作者：
Bird, Susan S.;Marur, Vasant R.;Sniatynski, Matthew J.;Greenberg, Heather K.;Kristal, Bruce S.
通讯作者：
Kristal, Bruce S.
影响因子：
25
作者：
de Anda, Froylan Calderon;Rosario, Ana Lucia;Durak, Omer;Tran, Tracy;Graeff, Johannes;Meletis, Konstantinos;Rei, Damien;Soda, Takahiro;Madabhushi, Ram;Ginty, David D.;Kolodkin, Alex L.;Tsai, Li-Huei
通讯作者：
Tsai, Li-Huei
影响因子：
16.6
作者：
Bayés À;Collins MO;Reig-Viader R;Gou G;Goulding D;Izquierdo A;Choudhary JS;Emes RD;Grant SG
通讯作者：
Grant SG
影响因子：
4.6
作者：
Gutzman, Jennifer H.;Sive, Hazel
通讯作者：
Sive, Hazel
影响因子：
0.9
作者：
Fetit, Rana;Price, David J.;Johnstone, Mandy
通讯作者：
Johnstone, Mandy