TDP-43 facilitates milk lipid secretion by post-transcriptional regulation of Btn1a1 and Xdh

Limin Zhao, Hao Ke, Haibo Xu, Guo Dong Wang, Honglei Zhang, Li Zou, Shu Xiang, Mengyuan Li, Li Peng, Mingfang Zhou, Lingling Li, Lei Ao, Qin Yang, Che Kun James Shen, Ping Yi, Lu Wang, Baowei Jiao

研究成果: 雜誌貢獻文章同行評審

3 引文 斯高帕斯(Scopus)

摘要

Milk lipid secretion is a critical process for the delivery of nutrition and energy from parent to offspring. However, the underlying molecular mechanism is less clear. Here we report that TDP-43, a RNA-binding protein, underwent positive selection in the mammalian lineage. Furthermore, TDP-43 gene (Tardbp) loss induces accumulation of large lipid droplets and severe lipid secretion deficiency in mammary epithelial cells to outside alveolar lumens, eventually resulting in lactation failure and pup starvation within three weeks postpartum. In human milk samples from lactating women, the expression levels of TDP-43 is positively correlated with higher milk output. Mechanistically, TDP-43 exerts post-transcriptional regulation of Btn1a1 and Xdh mRNA stability, which are required for the secretion of lipid droplets from epithelial cells to the lumen. Taken together, our results highlights the critical role of TDP-43 in milk lipid secretion, providing a potential strategy for the screening and intervention of clinical lactation insufficiency.

原文英語
文章編號341
期刊Nature Communications
11
發行號1
DOIs
出版狀態已發佈 - 十二月 1 2020
對外發佈

ASJC Scopus subject areas

  • 化學 (全部)
  • 生物化學、遺傳與分子生物學 (全部)
  • 物理與天文學 (全部)

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