Department of Chemistry, Faculty of Sciences, Kyushu University, Nishi-ku, Fukuoka 819-0395, Japan.
Department of Bioscience and Biotechnology, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Nishi-ku, Fukuoka 819-0395, Japan.
Mol Biol Cell. 2022 Oct 1;33(12):ar105. doi: 10.1091/mbc.E22-04-0117. Epub 2022 Jul 27.
Structural diversity of complex sphingolipids is important for maintenance of various cellular functions; however, the overall picture of the significance of this structural diversity remains largely unknown. To investigate the physiological importance of the structural diversity of complex sphingolipids, we here constructed a complex sphingolipid structural diversity disruption library in budding yeast, which comprises 11 mutants including with combinations of deletions of sphingolipid-metabolizing enzyme genes. The sensitivity of the mutants to various environmental stresses revealed that the more the structural variation of complex sphingolipids is limited, the more stress sensitivity tends to increase. Moreover, it was found that in mutant cells with only one subtype of complex sphingolipid, Slt2 MAP kinase and Msn2/4 transcriptional factors are essential for maintenance of a normal growth and compensation for reduced tolerance of multiple stresses caused by loss of complex sphingolipid diversity. Slt2 and Msn2/4 are involved in compensation for impaired integrity of cell walls and plasma membranes caused by loss of complex sphingolipid diversity, respectively. From these findings, it was suggested that loss of structural diversity of complex sphingolipids affects the environment of the cell surface, including both plasma membranes and cell walls, which could cause multiple environmental stress hypersensitivity.
复杂鞘脂的结构多样性对维持各种细胞功能很重要；然而，其结构多样性的重要性的全貌在很大程度上仍是未知的。为了研究复杂鞘脂结构多样性的生理重要性，我们在此构建了芽殖酵母中的复杂鞘脂结构多样性破坏文库，该文库包含 11 种突变体，包括鞘脂代谢酶基因缺失的组合。突变体对各种环境胁迫的敏感性表明，复杂鞘脂的结构变异越受限制，对胁迫的敏感性越容易增加。此外，发现只有一种复杂鞘脂亚型的突变体细胞中，Slt2 MAP 激酶和 Msn2/4 转录因子对于维持正常生长和补偿因复杂鞘脂多样性丧失而导致的多种应激耐受性降低是必需的。Slt2 和 Msn2/4 分别参与补偿复杂鞘脂多样性丧失导致的细胞壁和质膜完整性受损。从这些发现中可以推测，复杂鞘脂结构多样性的丧失会影响细胞表面的环境，包括质膜和细胞壁，这可能导致多种环境胁迫超敏性。
