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Phosphatidylserine enrichment in the nuclear membrane regulates key enzymes of phosphatidylcholine synthesis.
The EMBO Journal ( IF 9.4 ) Pub Date : 2024-06-25 , DOI: 10.1038/s44318-024-00151-z
Yang Niu 1 , Joshua G Pemberton 1 , Yeun Ju Kim 1 , Tamas Balla 1
Affiliation  

Phosphatidylserine (PS) is an important anionic phospholipid that is synthesized within the endoplasmic reticulum (ER). While PS shows the highest enrichment and serves important functional roles in the plasma membrane (PM) but its role in the nucleus is poorly explored. Using three orthogonal approaches, we found that PS is also uniquely enriched in the inner nuclear membrane (INM) and the nuclear reticulum (NR). Nuclear PS is critical for supporting the translocation of CCTα and Lipin1α, two key enzymes important for phosphatidylcholine (PC) biosynthesis, from the nuclear matrix to the INM and NR in response to oleic acid treatment. We identified the PS-interacting regions within the M-domain of CCTα and M-Lip domain of Lipin1α, and show that lipid droplet formation is altered by manipulations of nuclear PS availability. Our studies reveal an unrecognized regulatory role of nuclear PS levels in the regulation of key PC synthesizing enzymes within the nucleus.

中文翻译:


核膜中磷脂酰丝氨酸的富集调节磷脂酰胆碱合成的关键酶。



磷脂酰丝氨酸 (PS) 是一种重要的阴离子磷脂,在内质网 (ER) 内合成。虽然 PS 显示出最高的富集度并在质膜 (PM) 中发挥重要的功能作用,但其在细胞核中的作用却鲜为人知。使用三种正交方法,我们发现 PS 在内核膜 (INM) 和核网 (NR) 中也独特富集。核 PS 对于支持 CCTα 和 Lipin1α 的易位至关重要,CCTα 和 Lipin1α 是磷脂酰胆碱 (PC) 生物合成的两种重要酶,响应油酸处理,从核基质转移到 INM 和 NR。我们鉴定了 CCTα 的 M 结构域和 Lipin1α 的 M-Lip 结构域内的 PS 相互作用区域,并表明通过操纵核 PS 可用性可以改变脂滴的形成。我们的研究揭示了核 PS 水平在细胞核内关键 PC 合成酶调节中的未被认识到的调节作用。
更新日期:2024-06-25
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