ER-PM conetact欠損時にsynthetic lethal になる変異の探索 (Molecular Biology of the Cell 2020年4月8日号掲載論文)

結論から言うと、ER-PM接触部位を欠く酵母株の合成致死変異体をスクリーニングしてESCRT-III を同定した論文。


本日は「ESCRT-III and ER-PM contacts maintain lipid homeostasis (ESCRT-IIIとER-PM間MCSが脂質のホメオスタシスを維持する)」という論文で、米国 Weill Institute for Cell and Molecular Biology and Department of Molecular Biology and Genetics, Cornell University の Scott D. Emr のグループ(どういったラボ?→*1)による研究。(論文サイトへのlink→*2





Eukaryotic cells are compartmentalized into organelles by intracellular membranes. While the organelles are distinct, many of them make intimate contact with one another. These contacts were first observed in the 1950’s, but only recently have the functions of these contact sites begun to be understood. In yeast, the ER makes extensive inter-membrane contacts with the plasma membrane (PM), covering ∼40% of the PM. Many functions of ER-PM contacts have been proposed, including: non-vesicular lipid trafficking, ion transfer, and as signaling hubs. Surprisingly, cells that lack ER-PM contacts grow well, indicating that alternative pathways may be compensating for the loss of ER-PM contact. In order to better understand the function of ER-PM contact sites we used saturating transposon mutagenesis to identify synthetic lethal mutants in a yeast strain lacking ER-PM contact sites. The strongest hits were components of the ESCRT complexes. The synthetic lethal mutants have low levels of some lipid species but accumulate free fatty acids and lipid droplets. We found that only ESCRT-III components are synthetic lethal, indicating that Vps4 and other ESCRT complexes do not function in this pathway. These data suggest that ESCRT-III proteins and ER-PM contact sites act in independent pathways to maintain lipid homeostasis.



*1:--- The Emr lab studies the regulation of cell signaling pathways by phosphoinositide kinases, vesicle-mediated transport reactions, and selective ubiquitin modifications. --- より。もともとESCRTⅢを中心に研究しているグループのようです。