Hippo同功能基因SIK1调控拟南芥器官大小的机制

The regulation of organ size is a fundamental problem in developmental biology. In animals, the Hippo pathway restricts cell proliferation and promotes apoptosis to negatively regulate organ size. We had recently identified a Hippo ortholog, SIK1, in Arabidopsis, and demonstrated its function in promoting mitotic exit. Knock-out of SIK1 in Arabidopsis leads to reduced cell number, size, and endoreduplication in mature organs. Through a yeast two-hybrid screen, MOB1A and MOB1B were identified as SIK1-interacting partners. They turned out to be homologs of Mats--a scaffold protein for Hippo. The mob1a and sik1 mutants share similar phenotypes. The interaction between SIK1 and MOB1 is mediated by an N-terminal domain of SIK1. This domain is plant-specific, and also mediates the shuttle of SIK1 into the nucleus. Transcriptome analysis revealed significant changes in Jasmonate biosynthesis and signaling in the sik1 mutant. Based on these results, we seek to clarify how the nucleocytoplasmic shuttle of SIK1 is involved in its function in organ size determination, and to establish a direct link between SIK1 and Jasmonates. The potential outcomes will pave the way for constructing a complete Hippo pathway in plants.

器官大小调控是发育生物学的基本问题之一。在动物中，Hippo信号通路通过限制细胞增殖与促进细胞凋亡，负调控器官大小。我们前期在植物中首先找到了Hippo的同功能基因AtSIK1，证实了它促进细胞分裂退出的分子功能。SIK1敲除造成拟南芥成熟器官的细胞数量、大小、细胞核倍性下降，各器官显著变小。通过筛库找到了SIK1的脚手架蛋白MOB1，其与Hippo的脚手架蛋白Mats同源。mob1突变体与sik1表型相似。我们发现SIK1与MOB1的互作由植物SIK1特有的N-端结构域介导，该结构域同时介导SIK1从胞浆向细胞核的转移。转录分析表明sik1突变体中茉莉酸合成与信号转导发生了显著变化。在本项目中，我们计划探明SIK1入核对其调控器官大小的意义，并建立SIK1与JA途径的直接联系。研究结果将为构建完整的植物Hippo信号通路打下基础。

器官大小调控是生物学的基本问题之一，在癌症治疗、器官再生、作物增产方向有重要应用前景。2003年在果蝇中发现的Hippo通路是最重要的限制器官过度生长、促进凋亡的信号通路，其核心—蛋白激酶Hippo作为调控组织稳态的抑癌基因已被广泛研究。我们2015年在国际上首次发现植物也有Hippo通路，鉴定了拟南芥Hippo/SIK1及其支架蛋白MOB1，并证明了Hippo促进细胞分裂退出与细胞分化的分子功能在真核生物中保守。本项目发现SIK1作用于植物激素茉莉酸的信号通路关键组分，并建立了完整的植物Hippo信号通路。通过互换动、植物的Hippo，进一步确认Hippo通路在共同祖先中已经存在。同时还探索了动植物Hippo通路的相互关系。我们还发现，与动物不同，拟南芥SIK1存在强烈的剪切调控，其中一个剪切体单独存在时赋予植物生物量与抗逆两方面的优势，具有潜在应用价值。在项目支持下发表带标注通讯作者论文7篇，合作论文1篇，培养硕士毕业生4名。