The Receptor Kinases BAK1/SERK4 Regulate Ca2+ Channel-Mediated Cellular Homeostasis for Cell Death Containment

First author: Xiao Yu; Affiliations: Texas A&M University (德克萨斯A&M大学): TX, USA

Corresponding author: Libo Shan

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.

细胞死亡是一个重要的、并且很普遍的进程，在所有生物中都受到了严格的调控。然而，目前我们对于调控细胞死亡的精确机制还不够了解。作为植物生长、发育和免疫的一个重要模块，拟南芥受体激酶BAK1和体细胞胚胎发生受体激酶SERK4负调控植物细胞死亡，且相互之间存在功能冗余。作者通过一个基于RNAi技术遗传筛选bak1/serk4突变体细胞死亡的抑制子，发现了一个环核苷酸门控通道CNGC20作为超极化激活的钙离子渗透通道特异性调控bak1/serk4突变体的细胞死亡。BAK1能够直接与CNGC20碳端胞质结构域特定位点发生互作，并磷酸化该位点，从而调控CNGC20的稳定性。CNGC19，是CNGC20最近缘的同源蛋白，但相对丰度较低，在缺失CNGC20蛋白的情况下对于bak1/serk4突变体细胞死亡的调控发挥数量遗传调控，与CNGC20、CNGC19能够各自形成同聚体或一起形成异聚体通道复合物的生化结果一致。相比于野生型，bak1/serk4突变体中CNGC20和CNGC19基因的转录本有所增加，进一步说明了CNGC20和CNGC19的稳态在细胞死亡调控方面的重要作用。本文的研究不仅揭示了一个通过细胞表面驻留的受体激酶介导的磷酸化对离子通道稳定性的独特调控机制，同时还表明了通过形成同聚体和异聚体复合物，钙离子通道作用于细胞稳态维持的功能也有细微的差异。

通讯：Libo Shan (https://plantpathology.tamu.edu/people/shan-dr-libo/)

个人简介：北京师范大学，学士；堪萨斯州立大学，博士；哈佛医学院，博士后。

研究方向：寄主植物与微生物之间的互作。

doi: https://doi.org/10.1016/j.cub.2019.09.018

Journal: Current Biology

Published date: October 01, 2019