The maintenance of cellular phosphate(Pi)homeostasis is of great importance in living organisms.The SPX domain-containing protein 1(SPX1)proteins from both Arabidopsis and rice have been proposed to act as sensors of ...The maintenance of cellular phosphate(Pi)homeostasis is of great importance in living organisms.The SPX domain-containing protein 1(SPX1)proteins from both Arabidopsis and rice have been proposed to act as sensors of Pi status.The molecular signal indicating the cellular Pi status and regulating Pi homeostasis in plants,however,remains to be identified,as Pi itself does not bind to the SPX domain.Here,we report the identification of the inositol pyrophosphate lnsP8 as a signaling molecule that regulates Pi homeostasis in Arabidopsis.Polyacrylamide gel electrophoresis profiling of InsPs revealed that lnsP8 level positively correlates with cellular Pi concentration.We demonstrated that the homologs of diphosphoinositol pentaki-sphosphate kinase(PPIP5K),VIH1 and VIH2,function redundantly to synthesize lnsP8,and that the vih1 vih2 double mutant overaccumulates Pi.SPX1 directly interacts with PHR1,the central regulator of Pi starvation responses,to inhibit its function under Pi-replete conditions.However,this interaction is compromised in the vih1 vih2 double mutant,resulting in the constitutive induction of Pi starvation-induced genes,indicating that plant cells cannot sense cellular Pi status without lnsP8.Furthermore,we showed that lnsP8 could directly bind to the SPX domain of SPX1 and is essential for the interaction between SPX1 and PHR1.Collectively,our study suggests that lnsP8 is the intracellular Pi signaling molecule serving as the ligand of SPX1 for controlling Pi homeostasis in plants.展开更多
自闭症谱系障碍(autism spectrum disorder,ASD)是影响儿童精神健康最主要的一类神经发育障碍疾病,但致病机制尚不明确。人第10号染色体缺失并与张力蛋白同源的磷酸酶(phosphatase and tensin homolog on chromosome ten,PTEN),作为磷...自闭症谱系障碍(autism spectrum disorder,ASD)是影响儿童精神健康最主要的一类神经发育障碍疾病,但致病机制尚不明确。人第10号染色体缺失并与张力蛋白同源的磷酸酶(phosphatase and tensin homolog on chromosome ten,PTEN),作为磷脂酰肌醇3激酶(phosphatidylinositol 3-kinase,PI3K)信号通路重要的负调控因子,广泛参与到细胞生长、增殖和凋亡等生长发育的关键过程中。临床研究显示,部分ASD患者携带PTEN基因突变。PTEN基因突变引起PI3K通路过度激活,造成神经元形态和突触可塑性变化,是引起ASD的主要原因。因此,探索PTEN与ASD之间的关系,对揭示ASD发病机制、探索治疗方案具有积极的意义。本文对近年来PTEN突变在ASD患者和动物模型中的致病机制研究进行综述,提示PTEN-PI3K/AKT信号通路可能作为ASD重要的基因筛选位点和药物作用靶点。展开更多
文摘The maintenance of cellular phosphate(Pi)homeostasis is of great importance in living organisms.The SPX domain-containing protein 1(SPX1)proteins from both Arabidopsis and rice have been proposed to act as sensors of Pi status.The molecular signal indicating the cellular Pi status and regulating Pi homeostasis in plants,however,remains to be identified,as Pi itself does not bind to the SPX domain.Here,we report the identification of the inositol pyrophosphate lnsP8 as a signaling molecule that regulates Pi homeostasis in Arabidopsis.Polyacrylamide gel electrophoresis profiling of InsPs revealed that lnsP8 level positively correlates with cellular Pi concentration.We demonstrated that the homologs of diphosphoinositol pentaki-sphosphate kinase(PPIP5K),VIH1 and VIH2,function redundantly to synthesize lnsP8,and that the vih1 vih2 double mutant overaccumulates Pi.SPX1 directly interacts with PHR1,the central regulator of Pi starvation responses,to inhibit its function under Pi-replete conditions.However,this interaction is compromised in the vih1 vih2 double mutant,resulting in the constitutive induction of Pi starvation-induced genes,indicating that plant cells cannot sense cellular Pi status without lnsP8.Furthermore,we showed that lnsP8 could directly bind to the SPX domain of SPX1 and is essential for the interaction between SPX1 and PHR1.Collectively,our study suggests that lnsP8 is the intracellular Pi signaling molecule serving as the ligand of SPX1 for controlling Pi homeostasis in plants.
文摘自闭症谱系障碍(autism spectrum disorder,ASD)是影响儿童精神健康最主要的一类神经发育障碍疾病,但致病机制尚不明确。人第10号染色体缺失并与张力蛋白同源的磷酸酶(phosphatase and tensin homolog on chromosome ten,PTEN),作为磷脂酰肌醇3激酶(phosphatidylinositol 3-kinase,PI3K)信号通路重要的负调控因子,广泛参与到细胞生长、增殖和凋亡等生长发育的关键过程中。临床研究显示,部分ASD患者携带PTEN基因突变。PTEN基因突变引起PI3K通路过度激活,造成神经元形态和突触可塑性变化,是引起ASD的主要原因。因此,探索PTEN与ASD之间的关系,对揭示ASD发病机制、探索治疗方案具有积极的意义。本文对近年来PTEN突变在ASD患者和动物模型中的致病机制研究进行综述,提示PTEN-PI3K/AKT信号通路可能作为ASD重要的基因筛选位点和药物作用靶点。
