Cahoon Edgar B, Kim Panya, Xie Tian, González Solis Ariadna, Han Gongshe, Gong Xin, Dunn Teresa M
Center for Plant Science Innovation and Department of Biochemistry, University of Nebraska-Lincoln, Lincoln, NE 68588, USA.
Department of Chemical Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen 518055, China.
Plant Physiol. 2024 Dec 23;197(1). doi: 10.1093/plphys/kiae460.
Sphingolipid homeostatic regulation is important for balancing plant life and death. Plant cells finely tune sphingolipid biosynthesis to ensure sufficient levels to support growth through their basal functions as major components of endomembranes and the plasma membrane. Conversely, accumulation of sphingolipid biosynthetic intermediates, long-chain bases (LCBs) and ceramides, is associated with programmed cell death. Limiting these apoptotic intermediates is important for cell viability, while overriding homeostatic regulation permits cells to generate elevated LCBs and ceramides to respond to pathogens to elicit the hypersensitive response in plant immunity. Key to sphingolipid homeostasis is serine palmitoyltransferase (SPT), an endoplasmic reticulum-associated, multi-subunit enzyme catalyzing the first step in the biosynthesis of LCBs, the defining feature of sphingolipids. Across eukaryotes, SPT interaction with its negative regulator Orosomucoid-like (ORM) is critical for sphingolipid biosynthetic homeostasis. The recent cryo-electron microscopy structure of the Arabidopsis SPT complex indicates that ceramides bind ORMs to competitively inhibit SPT activity. This system provides a sensor for intracellular ceramide concentrations for sphingolipid homeostatic regulation. Combining the newly elucidated Arabidopsis SPT structure and mutant characterization, we present a model for the role of the 2 functionally divergent Arabidopsis ceramide synthase classes to produce ceramides that form repressive (trihydroxy LCB-ceramides) or nonrepressive (dihydroxy LCB-ceramides) ORM interactions to influence SPT activity. We describe how sphingolipid biosynthesis is regulated by the interplay of ceramide synthases with ORM-SPT when "enough is enough" and override homeostatic suppression when "enough is not enough" to respond to environmental stimuli such as microbial pathogen attack.
鞘脂稳态调节对于平衡植物的生死至关重要。植物细胞精细调节鞘脂生物合成，以确保有足够水平来支持生长，因为它们作为内膜和质膜的主要成分发挥着基础功能。相反，鞘脂生物合成中间体、长链碱（LCBs）和神经酰胺的积累与程序性细胞死亡相关。限制这些凋亡中间体对于细胞活力很重要，而超越稳态调节则允许细胞产生升高的LCBs和神经酰胺，以应对病原体，引发植物免疫中的超敏反应。鞘脂稳态的关键是丝氨酸棕榈酰转移酶（SPT），这是一种与内质网相关的多亚基酶，催化LCBs生物合成的第一步，而LCBs是鞘脂的决定性特征。在整个真核生物中，SPT与其负调节因子类orosomucoid（ORM）的相互作用对于鞘脂生物合成稳态至关重要。拟南芥SPT复合物最近的冷冻电子显微镜结构表明，神经酰胺与ORM结合以竞争性抑制SPT活性。该系统为鞘脂稳态调节提供了一种细胞内神经酰胺浓度传感器。结合新阐明的拟南芥SPT结构和突变体表型分析，我们提出了一个模型，阐述了拟南芥中2种功能不同的神经酰胺合酶类别的作用，即产生形成抑制性（三羟基LCB-神经酰胺）或非抑制性（二羟基LCB-神经酰胺）ORM相互作用的神经酰胺，以影响SPT活性。我们描述了鞘脂生物合成如何在“足够就够”时由神经酰胺合酶与ORM-SPT的相互作用进行调节，而在“不够”时超越稳态抑制，以应对诸如微生物病原体攻击等环境刺激。
