Feldman Maximilian J, Poirier Brenton C, Lange B Markus
Donald Danforth Plant Science Center, 975 North Warson Road, St. Louis, MO, 63132, USA.
Planta. 2015 Oct;242(4):921-33. doi: 10.1007/s00425-015-2322-4. Epub 2015 May 26.
Misexpression of the AtNPC1 - 1 and AtNPC1 - 2 genes leads to altered sphingolipid metabolism, growth impairment, and male reproductive defects in a hemizygous Arabidopsis thaliana (L.) double-mutant population. Abolishing the expression of both gene copies has lethal effects. Niemann-Pick disease type C1 is a lysosomal storage disorder caused by mutations in the NPC1 gene. At the cellular level, the disorder is characterized by the accumulation of storage lipids and lipid trafficking defects. The Arabidopsis thaliana genome contains two genes (At1g42470 and At4g38350) with weak homology to mammalian NPC1. The corresponding proteins have 11 predicted membrane-spanning regions and contain a putative sterol-sensing domain. The At1g42470 protein is localized to the plasma membrane, while At4g38350 protein has a dual localization in the plasma and tonoplast membranes. A phenotypic analysis of T-DNA insertion mutants indicated that At1g42470 and At4g38350 (designated AtNPC1-1 and AtNPC1-2, respectively) have partially redundant functions and are essential for plant reproductive viability and development. Homozygous plants impaired in the expression of both genes were not recoverable. Plants of a hemizygous AtNPC1-1/atnpc1-1/atnpc1-2/atnpc1-2 population were severely dwarfed and exhibited male gametophytic defects. These gene disruptions did not have an effect on sterol concentrations; however, hemizygous AtNPC1-1/atnpc1-1/atnpc1-2/atnpc1-2 mutants had increased fatty acid amounts. Among these, fatty acid α-hydroxytetracosanoic acid (h24:0) occurs in plant sphingolipids. Follow-up analyses confirmed the accumulation of significantly increased levels of sphingolipids (assayed as hydrolyzed sphingoid base component) in the hemizygous double-mutant population. Certain effects of NPC1 misexpression may be common across divergent lineages of eukaryotes (sphingolipid accumulation), while other defects (sterol accumulation) may occur only in certain groups of eukaryotic organisms.
拟南芥（L.）半合子双突变群体中，AtNPC1 - 1和AtNPC1 - 2基因的错误表达会导致鞘脂代谢改变、生长受损以及雄性生殖缺陷。消除两个基因拷贝的表达具有致死效应。1型尼曼 - 皮克病是一种由NPC1基因突变引起的溶酶体贮积症。在细胞水平上，该病症的特征是贮存脂质的积累和脂质运输缺陷。拟南芥基因组包含两个与哺乳动物NPC1具有弱同源性的基因（At1g42470和At4g38350）。相应的蛋白质有11个预测的跨膜区域，并包含一个假定的固醇感应结构域。At1g42470蛋白定位于质膜上，而At4g38350蛋白在质膜和液泡膜上具有双重定位。对T-DNA插入突变体的表型分析表明，At1g42470和At4g38350（分别命名为AtNPC1-1和AtNPC1-2）具有部分冗余功能，并且对植物生殖活力和发育至关重要。两个基因表达均受损的纯合植物无法存活。半合子AtNPC1-1/atnpc1-1/atnpc1-2/atnpc1-2群体的植株严重矮化，并表现出雄配子体缺陷。这些基因破坏对固醇浓度没有影响；然而，半合子AtNPC1-1/atnpc1-1/atnpc1-2/atnpc1-2突变体的脂肪酸含量增加。其中，脂肪酸α-羟基二十四烷酸（h24:0）存在于植物鞘脂中。后续分析证实，半合子双突变群体中鞘脂水平显著升高（以水解鞘氨醇碱成分测定）。NPC1错误表达的某些影响可能在不同的真核生物谱系中是常见的（鞘脂积累），而其他缺陷（固醇积累）可能仅发生在某些真核生物群体中。
