The Receptor Kinases BAK1/SERK4 Regulate Ca2+ Channel-Mediated Cellular Homeostasis for Cell Death Containment
The Receptor Kinases BAK1/SERK4 Regulate Ca2+ Channel-Mediated Cellular Homeostasis for Cell Death Containment
复制标题
受体激酶 BAK1/SERK4 调节 Ca2 通道介导的细胞稳态以抑制细胞死亡
DOI：
10.1016/j.cub.2019.09.018
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发表时间：
2019-11-18
期刊：
影响因子：
9.2
通讯作者：
Shan, Libo
中科院分区：
文献类型：
--
作者：
Yu, Xiao;Xu, Guangyuan;Shan, Libo
细胞死亡是一个重要而普遍的过程，在所有生物体中都受到严格控制。然而，精确的细胞死亡控制的机制仍然支离破碎。作为植物生长、发育和免疫的重要共享模块，拟南芥油菜素类固醇不敏感1相关受体蛋白1(BAK1)和体细胞胚胎发生受体蛋白4(SERK4)冗余和负性调节植物细胞死亡。通过部署基于RNAi的bak1/serk4细胞死亡抑制基因筛查，我们揭示了环核苷酸门控通道20(CNGC20)作为一种超极化激活的钙渗透通道，特异性地调节bak1/serk4细胞死亡。BAK1直接与CNGC20在C端胞浆结构域的特定位点相互作用并磷酸化，进而调节CNGC20的稳定性。CNGC19是与CNGC20最接近的同源物，与CNGC20相比丰度较低，只有在没有CNGC20的情况下，它才对bak1/serk4细胞的死亡做出了定量的遗传贡献，支持了CNGC20和CNGC19通道复合体的同质和异构体组装的生化数据。与野生型植物相比，在bak1/serk4中CNGC20和CNGC19的转录增加，进一步证实了CNGC20和CNGC19的动态平衡在细胞死亡控制中的关键作用。我们的研究不仅揭示了细胞表面驻留受体激酶介导的磷酸化对离子通道稳定性的独特调节，而且为通过形成同源和异源四聚体复合体来微调钙通道在维持细胞内稳中的作用提供了证据。
Cell death is a vital and ubiquitous process that is tightly controlled in all organisms. However, the mechanisms underlying precise cell death control remain fragmented. As an important shared module in plant growth, development, and immunity, Arabidopsis thaliana BRASSINOSTEROID INSENSITIVE 1-associated receptor kinase 1 (BAK1) and somatic embryogenesis receptor kinase 4 (SERK4) redundantly and negatively regulate plant cell death. By deploying an RNAi-based genetic screen for bak1/serk4 cell death suppressors, we revealed that cyclic nucleotide-gated channel 20 (CNGC20) functions as a hyperpolarization-activated Ca2+-permeable channel specifically regulating bak1/serk4 cell death. BAK1 directly interacts with and phosphorylates CNGC20 at specific sites in the C-terminal cytosolic domain, which in turn regulates CNGC20 stability. CNGC19, the closest homolog of CNGC20 with a low abundance compared with CNGC20, makes a quantitative genetic contribution to bak1/serk4 cell death only in the absence of CNGC20, supporting the biochemical data showing homo-and heteromeric assembly of the CNGC20 and CNGC19 channel complexes. Transcripts of CNGC20 and CNGC19 are elevated in bak1/serk4 compared with wild-type plants, further substantiating a critical role of homeostasis of CNGC20 and CNGC19 in cell death control. Our studies not only uncover a unique regulation of ion channel stability by cell-surface-resident receptor kinase-mediated phosphorylation but also provide evidence for fine-tuning Ca2+ channel functions in maintaining cellular homeostasis by the formation of homo-and heterotetrameric complexes.