2018年1月10日Nature在线发表了题目为“An extracellular network of Arabidopsis leucine-rich repeat receptor kinases”的文章。该文章介绍了利用高灵敏，高通量互作分析方法，建立了拟南芥富含亮氨酸重复类受体蛋白激酶（LRR-RLKs）互作网络。

多细胞生物体的细胞使用表面受体接受细胞外信号。细胞表面受体的胞外结构域（ECDs）作为蛋白互作的平台，并作为受体激活的调控模块。理解ECDs之间的相互作用如何产生有信号能力的受体复合物是具有挑战性的，因为它们在生化上难以处理。在植物中，由于受体家族的大量扩增，为受体相互作用的变化创造了巨大的潜力，因此ECD相互作用的发现变得更加复杂。拟南芥中，这些家族中最大的一个是由225个进化相关的富含亮氨酸的重复受体激酶（LRR-RK）组成，其在微生物的感应，细胞扩增，气孔发育和干细胞维持中起作用。尽管调控LRR-RK信号激活的原理正在变得清晰，但这个蛋白质家族的系统级的组织还是未知的。在这里，为了解决这个问题，我们使用高敏感高通量相互作用分析法，研究了4万个潜在的ECD相互作用，并且构建了由567个相互作用组成的，基于LRR的细胞表面相互作用网络（CSILRR）。为了证明CSILRR检测生物相关相互作用的能力，我们预测和验证了未经鉴定的LRR-RK在植物生长和免疫中的功能。此外，CSILRR作为一个统一的调控网络运作，其中LRR-RK对其总体结构最为关键，以防止几个网络步骤外的受体的异常信号传导。因此，植物已经进化了LRR-RK网络，从而正确的调节细胞外信号，保证其响应的平衡。

The cells of multicellular organisms receive extracellular signals using surface receptors. The extracellular domains (ECDs) of cell surface receptors function as interaction platforms, and as regulatory modules of receptor activation. Understanding how interactions between ECDs produce signal-competent receptor complexes is challenging because of their low biochemical tractability. In plants, the discovery of ECD interactions is complicated by the massive expansion of receptor families, which creates tremendous potential for changeover in receptor interactions. The largest of these families in Arabidopsis thaliana consists of 225 evolutionarily related leucine-rich repeat receptor kinases (LRR-RKs), which function in the sensing of microorganisms, cell expansion, stomata development and stem-cell maintenance. Although the principles that govern LRR-RK signalling activation are emerging, the systems-level organization of this family of proteins is unknown. Here, to address this, we investigated 40,000 potential ECD interactions using a sensitized high-throughput interaction assay, and produced an LRR-based cell surface interaction network (CSILRR) that consists of 567 interactions. To demonstrate the power of CSILRR for detecting biologically relevant interactions, we predicted and validated the functions of uncharacterized LRR-RKs in plant growth and immunity. In addition, we show that CSILRR operates as a unified regulatory network in which the LRR-RKs most crucial for its overall structure are required to prevent the aberrant signalling of receptors that are several network-steps away. Thus, plants have evolved LRR-RK networks to process extracellular signals into carefully balanced responses.

CSILRR is defined by four distinct subnetworks and two critical nodes

WalkTrap subnetworks are shown in orange