在973计划的支持下，“神经分化各阶段细胞命运决定的调控网络研究及其转化应用”项目取得重要进展，发现了细胞感受外界环境变化并做出反应的关键分子及其作用机制。
生物体总是处于不断变化的细胞内外环境中，譬如温度、细胞内外酸碱度及渗透压等。所有生物体都需要感受这些不断变化的内外界环境并做出相应的反应，以维持细胞正常的生理功能。但是，细胞如何对环境变化做出反应并不清楚。同济大学章小清教授研究团队发现了可以感受温度、细胞外酸碱度及渗透压变化的转录因子Smad5，当细胞外环境发生变化时，Smad5可以迅速捕捉到胞内酸碱度的细微变化，通过核浆穿梭来调节细胞内能量稳态。敲除Smad5会引起细胞内能量稳态的紊乱并干扰正常发育过程。
这是首次发现细胞如何回应外界环境变化，维持细胞内代谢稳态的机理，深化了人们对细胞内酸碱度和代谢稳态建立及维持的理解，为药物研发、细胞移植及治疗奠定了基础。相关研究结果在2017年7月Cell
Research杂志上发表。
英文摘要：
Both environmental cues and intracellular bioenergetic states profoundly affect intracellular pH (pHi). How a cell responds to pHi changes to maintain bioenergetic homeostasis remains elusive. Here we show that Smad5, a well-characterized downstream component of bone morphogenetic protein (BMP) signaling responds to pHi changes. Cold, basic or hypertonic conditions increase pHi, which in turn dissociates protons from the charged amino acid clusters within the MH1 domain of Smad5, prompting its relocation from the nucleus to the cytoplasm. On the other hand, heat, acidic or hypotonic conditions decrease pHi, blocking the nuclear export of Smad5, and thus causing its nuclear accumulation. Active nucleocytoplasmic shuttling of Smad5 induced by environmental changes and pHi fluctuation is independent of BMP signaling, carboxyl terminus phosphorylation and Smad4. In addition, ablation of Smad5 causes chronic and irreversible dysregulation of cellular bioenergetic homeostasis and disrupted normal neural developmental processes as identified in a differentiation model of human pluripotent stem cells. Importantly, these metabolic and developmental deficits in Smad5-deficient cells could be rescued only by cytoplasmic Smad5. Cytoplasmic Smad5 physically interacts with hexokinase 1 and accelerates glycolysis. Together, our findings indicate that Smad5 acts as a pHi messenger and maintains the bioenergetic homeostasis of cells by regulating cytoplasmic metabolic machinery.
原文阅读：Smad5 acts as an intracellular pH messenger and maintains bioenergetic homeostasis
Cell：细胞治疗领域观察者
长按识别二维码，轻松关注
