Section on Molecular Signal Transduction, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 20892, USA.
EMBO J. 2024 Aug;43(16):3414-3449. doi: 10.1038/s44318-024-00151-z. Epub 2024 Jun 25.
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.
磷脂酰丝氨酸（PS）是一种重要的阴离子磷脂，在内质网（ER）中合成。PS 虽然在质膜（PM）中含量最高且具有重要的功能作用，但它在核内的作用尚未得到充分研究。我们使用三种正交方法发现，PS 在内核膜（INM）和核网（NR）中也有独特的富集。核 PS 对于支持 CCTα 和 Lipin1α 的易位至关重要，CCTα 和 Lipin1α 是两种对磷脂酰胆碱（PC）生物合成至关重要的关键酶，它们响应油酸处理从核基质到 INM 和 NR。我们确定了 CCTα 的 M 结构域和 Lipin1α 的 M-Lip 结构域中与 PS 相互作用的区域，并表明通过操纵核 PS 的可用性会改变脂滴的形成。我们的研究揭示了核 PS 水平在核内关键 PC 合成酶调节中的未被认识的调节作用。
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