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营养传感器CRTC和Sarcalumenin/thinman代表了心脏缩的一个替代途径

Cristiana Dondi¹, Georg Vogler¹, Anjali Gupta¹

¹Development, Aging and Regeneration Program, Center for Genetic Disorders and Aging Research, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.

|August 2, 2024

概括

通过CREB调节的转录共激活剂 (CRTC) 在心脏缩中起着关键作用. 这项研究揭示了在多个模型系统中对心脏功能至关重要的一种保存的Calcineurin-CRTC-Sarcalumenin信号通路.

科学领域:

心脏病学心脏病学
分子生物学分子生物学
遗传学遗传学是一种遗传学.

背景情况:

已知氨酸 (CaN) 调节葡萄糖生成基因,并与心脏缩有关.
对于CREB调节的转录共激活剂 (CRTC) 在心脏功能中的作用,特别是在心脏缩方面,仍然在很大程度上未被探索.

研究的目的:

研究CRTC在心脏缩中的心脏自主作用.
阐明涉及CRTC在心脏功能中的分子机制和信号通路.

主要方法:

使用Drosophila melanogaster作为研究CRTC突变体和心脏特异性敲击/过度表达的模型系统.
在CRTC操纵的Drosophila心脏上进行RNA测序 (RNA-seq).
在斑马鱼和人类诱导心肌细胞中研究了CRTC的敲击.

主要成果:

在Drosophila的心脏中,CRTC突变和敲击显示了心脏限制,肌纤维细胞失调,纤维化和低心率.
在Drosophila中,心脏特异性的CRTC过度表达导致过度缩.
在CRTC突变体中,CaN诱导的缩减少,这表明CRTC的调解作用.
RNA-seq确定了代谢基因失调,并突出显示了sarcalumenin (Srl) 作为下游目标.
在斑马鱼和人类心肌细胞中的CRTC操纵重复了心脏功能障碍,并影响了Srl表达和作用潜力的持续时间.

结论:

CRTC在调节心脏缩方面发挥着重要的心脏自主作用.
一个涉及氨酸-CRTC-sarcalumenin的保存信号通路被确定为对心脏功能和缩至关重要的.
这一途径代表了理解和潜在治疗心脏病的新目标.

关键词:

CP: 细胞生物学细胞生物学 CP:新陈代谢过程中的新陈代谢.在CRTC中,CRTC可以使用CRTC.氨酸是氨酸中的一种.这种植物是Drosophila.这是sarcalumenin.这是心脏病,心脏病.纤维化纤维化这种细胞是hiPSC-心肌细胞.过度缩的过度缩是一个问题.瘦人瘦人瘦人斑马鱼是一种斑马鱼.

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