A Chemical Genetics Approach Reveals H,K-ATPase-Mediated Membrane Voltage Is Required for Planarian Head Regeneration

被引:148
作者
Beane, Wendy S.
Morokuma, Junji
Adams, Dany S.
Levin, Michael [1 ]
机构
[1] Tufts Univ, Dept Biol, Medford, MA 02155 USA
来源
CHEMISTRY & BIOLOGY | 2011年 / 18卷 / 01期
基金
美国国家科学基金会;
关键词
LEFT-RIGHT ASYMMETRY; CALCIUM-CHANNELS; K+ CHANNEL; STEM-CELLS; ATPASE; H+; LOCALIZATION; EXPRESSION; POLARITY; KIR4.1;
D O I
10.1016/j.chembiol.2010.11.012
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:77 / 89
页数:13
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