Abstract：
The ability to sense and respond to osmotic fluctuations is critical for the maintenance of cellular integrity. We used gene co-essentiality analysis to identify an unappreciated relationship between TSC22D2, WNK1, and NRBP1 in regulating cell volume homeostasis. All of these genes have paralogs and are functionally buffered for osmo-sensing and cell volume control. Within seconds of hyperosmotic stress, TSC22D, WNK, and NRBP family members physically associate into biomolecular condensates, a process that is dependent on intrinsically disordered regions (IDRs). A close examination of these protein families across metazoans revealed that TSC22D genes evolved alongside a domain in NRBPs that specifically binds to TSC22D proteins, which we have termed NbrT (NRBP binding region with TSC22D), and this co-evolution is accompanied by rapid IDR length expansion in WNK-family kinases. Our study reveals that TSC22D, WNK, and NRBP genes evolved in metazoans to co-regulate rapid cell volume changes in response to osmolarity.
摘要：
感知和响应渗透波动的能力对于维持细胞完整性至关重要。我们使用基因共质分析来确定TSC22D2，WNK1和NRBP1在调节细胞体积稳态方面的未被理解的关系。所有这些基因都具有旁系同源物，并且在功能上被缓冲以进行渗透感应和细胞体积控制。在高渗应激的几秒钟内，TSC22D,WNK,和NRBP家族成员物理缔合成生物分子缩合物，一个依赖于内在无序区域(IDR)的过程。对后生动物的这些蛋白质家族的仔细检查表明，TSC22D基因与NRBPs中的一个结构域一起进化，该结构域与TSC22D蛋白特异性结合，我们称之为NbrT（NRBP与TSC22D结合区），这种共同进化伴随着WNK家族激酶中IDR长度的快速扩展。我们的研究表明，TSC22D，WNK,和NRBP基因在后生动物中进化，以共同调节响应渗透压的快速细胞体积变化。
