Phospholipid biogenesis maintains neuronal integrity during aging and axon regeneration.

IF 3.3 3区生物学 Q2 GENETICS & HEREDITY

Genetics Pub Date : 2025-06-25 DOI:10.1093/genetics/iyaf122

Seungmee Park, Yishi Jin, Andrew D Chisholm

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引用次数: 0

Abstract

Neurons maintain their morphology over prolonged periods of adult life with limited regenerative capacity. Among the various factors that shape neuronal morphology, lipids function as membrane components, signaling molecules, and regulators of synaptic plasticity. Here, we tested genes involved in phospholipid biosynthesis and identified their roles in axon regrowth and maintenance. CEPT-2 and EPT-1 are enzymes catalyzing the final steps in the de novo phospholipid synthesis (Kennedy) pathway. Loss of function mutants of cept-2 or ept-1 show reduced axon regrowth and failure to maintain axon morphology. We demonstrate that CEPT-2 is required cell-autonomously to prevent age-related axonal morphology defects. We further investigated genetic interactions of cept-2 or ept-1 with dip-2, a conserved regulator of lipid metabolism that affects axon morphology maintenance and regrowth after injury. Loss of function in dip-2 led to suppression of axon regrowth defects observed in either cept-2 or ept-2 mutants, suggesting that DIP-2 acts to counterbalance phospholipid synthesis. Our findings reveal the genetic regulation of lipid metabolism as critical for axon maintenance following injury and during aging.

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磷脂生物发生在衰老和轴突再生过程中维持神经元的完整性。

在有限的再生能力下，神经元在长时间的成年生活中保持其形态。在形成神经元形态的各种因素中，脂质作为膜成分、信号分子和突触可塑性的调节剂发挥作用。在这里，我们测试了参与磷脂生物合成的基因，并确定了它们在轴突再生和维持中的作用。ept -2和EPT-1是催化新生磷脂合成（Kennedy）途径最后步骤的酶。功能缺失的突变体cpt -2或ept-1显示轴突再生减少和不能维持轴突形态。我们证明CEPT-2是细胞自主所需的，以防止与年龄相关的轴突形态缺陷。我们进一步研究了cpt -2或cpt -1与dip-2的遗传相互作用，dip-2是一种保守的脂质代谢调节因子，影响损伤后轴突形态维持和再生。dip-2的功能缺失导致cpt -2或ept-2突变体的轴突再生缺陷受到抑制，这表明dip-2起到了平衡磷脂合成的作用。我们的研究结果揭示了脂质代谢的遗传调控对于损伤后和衰老过程中的轴突维持至关重要。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Genetics GENETICS & HEREDITY-

CiteScore

6.90

自引率

6.10%

发文量

177

审稿时长

1.5 months

期刊介绍： GENETICS is published by the Genetics Society of America, a scholarly society that seeks to deepen our understanding of the living world by advancing our understanding of genetics. Since 1916, GENETICS has published high-quality, original research presenting novel findings bearing on genetics and genomics. The journal publishes empirical studies of organisms ranging from microbes to humans, as well as theoretical work. While it has an illustrious history, GENETICS has changed along with the communities it serves: it is not your mentor''s journal. The editors make decisions quickly – in around 30 days – without sacrificing the excellence and scholarship for which the journal has long been known. GENETICS is a peer reviewed, peer-edited journal, with an international reach and increasing visibility and impact. All editorial decisions are made through collaboration of at least two editors who are practicing scientists. GENETICS is constantly innovating: expanded types of content include Reviews, Commentary (current issues of interest to geneticists), Perspectives (historical), Primers (to introduce primary literature into the classroom), Toolbox Reviews, plus YeastBook, FlyBook, and WormBook (coming spring 2016). For particularly time-sensitive results, we publish Communications. As part of our mission to serve our communities, we''ve published thematic collections, including Genomic Selection, Multiparental Populations, Mouse Collaborative Cross, and the Genetics of Sex.