一种化学遗传学方法揭示了涡虫头部再生需要H，K-ATP酶介导的膜电压。
A chemical genetics approach reveals H,K-ATPase-mediated membrane voltage is required for planarian head regeneration.
作者信息
Beane Wendy S, Morokuma Junji, Adams Dany S, Levin Michael
机构信息
Biology Department and Tufts Center for Regenerative and Developmental Biology, Tufts University, Medford, MA 02155-4243, USA.
出版信息
Chem Biol. 2011 Jan 28;18(1):77-89. doi: 10.1016/j.chembiol.2010.11.012.
Biophysical signaling is required for both embryonic polarity and regenerative outgrowth. Exploiting endogenous ion transport for regenerative therapies will require direct regulation of membrane voltage. Here, we develop a pharmacological method to target ion transporters, uncovering a role for membrane voltage as a key regulator of anterior polarity in regenerating planaria. Utilizing the highly specific inhibitor, SCH-28080, our data reveal that H(+),K(+)-ATPase-mediated membrane depolarization is essential for anterior gene expression and brain induction. H(+),K(+)-ATPase-independent manipulation of membrane potential with ivermectin confirms that depolarization drives head formation, even at posterior-facing wounds. Using this chemical genetics approach, we demonstrate that membrane voltage controls head-versus-tail identity during planarian regeneration. Our data suggest well-characterized drugs (already approved for human use) might be exploited to control adult stem cell-driven pattern formation during the regeneration of complex structures.
生物物理信号传导对于胚胎极性和再生生长都是必需的。利用内源性离子转运进行再生治疗将需要直接调节膜电压。在这里，我们开发了一种靶向离子转运体的药理学方法，揭示了膜电压作为再生涡虫前极性关键调节因子的作用。利用高度特异性抑制剂SCH-28080，我们的数据表明，H(+)，K(+)-ATP酶介导的膜去极化对于前部基因表达和脑诱导至关重要。用伊维菌素对膜电位进行H(+)，K(+)-ATP酶非依赖性操作证实，去极化驱动头部形成，即使在面向后部的伤口处也是如此。使用这种化学遗传学方法，我们证明了膜电压在涡虫再生过程中控制头部与尾部的身份。我们的数据表明，特征明确的药物（已批准用于人类）可能被用于控制复杂结构再生过程中成年干细胞驱动的模式形成。
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