Ohsaki Yuki, Kawai Takeshi, Yoshikawa Yukichika, Cheng Jinglei, Jokitalo Eija, Fujimoto Toyoshi
Department of Anatomy and Molecular Cell Biology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
Electron Microscopy Unit, Institute of Biotechnology, University of Helsinki, 00014 Helsinki, Finland.
J Cell Biol. 2016 Jan 4;212(1):29-38. doi: 10.1083/jcb.201507122.
Lipid droplets (LDs) in the nucleus of hepatocyte-derived cell lines were found to be associated with premyelocytic leukemia (PML) nuclear bodies (NBs) and type I nucleoplasmic reticulum (NR) or the extension of the inner nuclear membrane. Knockdown of PML isoform II (PML-II) caused a significant decrease in both nuclear LDs and type I NR, whereas overexpression of PML-II increased both. Notably, these effects were evident only in limited types of cells, in which a moderate number of nuclear LDs exist intrinsically, and PML-II was targeted not only at PML NBs, but also at the nuclear envelope, excluding lamins and SUN proteins. Knockdown of SUN proteins induced a significant increase in the type I NR and nuclear LDs, but these effects were cancelled by simultaneous knockdown of PML-II. Nuclear LDs harbored diacylglycerol O-acyltransferase 2 and CTP:phosphocholine cytidylyltransferase α and incorporated newly synthesized lipid esters. These results corroborated that PML-II plays a critical role in generating nuclear LDs in specific cell types.
在肝细胞衍生的细胞系细胞核中发现的脂滴(LDs)与早幼粒细胞白血病(PML)核体(NBs)以及I型核质网(NR)或内核膜的延伸有关。敲低PML亚型II(PML-II)会导致核脂滴和I型核质网显著减少,而PML-II的过表达则会使两者都增加。值得注意的是,这些效应仅在有限类型的细胞中明显,这些细胞内源性地存在适度数量的核脂滴,并且PML-II不仅靶向PML核体,还靶向核膜,不包括核纤层蛋白和SUN蛋白。敲低SUN蛋白会导致I型核质网和核脂滴显著增加,但这些效应会被同时敲低PML-II所抵消。核脂滴含有二酰基甘油O-酰基转移酶2和CTP:磷酸胆碱胞苷转移酶α,并掺入新合成的脂质酯。这些结果证实,PML-II在特定细胞类型中核脂滴的生成中起关键作用。