Regulation of maternal phospholipid composition and IP3-dependent embryonic membrane dynamics by a specific fatty acid metabolic event in C. elegans
Regulation of maternal phospholipid composition and IP3-dependent embryonic membrane dynamics by a specific fatty acid metabolic event in C. elegans
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DOI：
10.1101/gad.187054.112
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发表时间：
2012-03-15
影响因子：
10.5
通讯作者：
Han, Min
中科院分区：
文献类型：
--
作者：
Kniazeva, Marina;Shen, Huali;Han, Min
天然脂肪酸（FAs）表现出巨大的结构多样性，但FA变异的功能重要性以及它们对动物健康脂质组成的作用机制在很大程度上仍未被探索。一个大的酰基辅酶A合成酶家族（ACSs）通过将FA酯化成辅酶A来调节FA代谢。然而，对于特定的FA- acs组合如何影响脂质组成和特定的细胞功能，我们知之甚少。我们分析了支链FA C17ISO上ACS-1的活性如何影响母体脂质含量、信号转导和线虫胚胎的发育。我们发现，体细胞性腺中ACS-1的表达引导C17ISO与某些磷脂的结合，从而调节合子中的磷脂组成。破坏这种ACS-1功能会导致复杂的膜动力学出现显著缺陷，包括胞吐和胞质分裂，从而导致早期胚胎死亡。这些缺陷被过度活跃的IP3信号所抑制，这表明C17ISO和ACS-1功能是早期胚胎发生所必需的最佳IP3信号的必要条件。本研究揭示了支链FAs的新作用，其在人类和动物中的功能尚不清楚，并揭示了一种新的细胞间调节途径，将特定的FA-ACS相互作用与特定的发育事件联系起来。
Natural fatty acids (FAs) exhibit vast structural diversity, but the functional importance of FA variations and the mechanism by which they contribute to a healthy lipid composition in animals remain largely unexplored. A large family of acyl-CoA synthetases (ACSs) regulates FA metabolism by esterifying FA to coenyzme A. However, little is known about how particular FA-ACS combinations affect lipid composition and specific cellular functions. We analyzed how the activity of ACS-1 on branched chain FA C17ISO impacts maternal lipid content, signal transduction, and development in Caenorhabditis elegans embryos. We show that expression of ACS-1 in the somatic gonad guides the incorporation of C17ISO into certain phospholipids and thus regulates the phospholipid composition in the zygote. Disrupting this ACS-1 function causes striking defects in complex membrane dynamics, including exocytosis and cytokinesis, leading to early embryonic lethality. These defects are suppressed by hyperactive IP3 signaling, suggesting that C17ISO and ACS-1 functions are necessary for optimal IP3 signaling essential for early embryogenesis. This study shows a novel role of branched chain FAs whose functions in humans and animals are unknown and uncovers a novel intercellular regulatory pathway linking a specific FA-ACS interaction to specific developmental events.