期刊
NATURE COMMUNICATIONS
卷 12, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-26177-z
关键词
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资金
- Ministry of Education, Singapore, under its Academic Research Fund Tier 2 Award [MOE2017-T2-2-001]
- Ministry of Education, Singapore, under Academic Research Fund Tier 1 Award [2018-T1-001-023]
- Nanyang Assistant Professorship (NAP)
- Lee Kong Chian School of Medicine startup grant (LKCMedicine-SUG)
- Japanese Society for Promotion of Science
Cellular membranes have unique lipid compositions, and cells maintain endosomal lipid homeostasis through lipid transfer proteins and phosphatases to prevent the accumulation of PI(4,5)P-2 on endosomes.
Different types of cellular membranes have unique lipid compositions that are important for their functional identity. PI(4,5)P-2 is enriched in the plasma membrane where it contributes to local activation of key cellular events, including actomyosin contraction and cytokinesis. However, how cells prevent PI(4,5)P-2 from accumulating in intracellular membrane compartments, despite constant intermixing and exchange of lipid membranes, is poorly understood. Using the C. elegans early embryo as our model system, we show that the evolutionarily conserved lipid transfer proteins, PDZD-8 and TEX-2, act together with the PI(4,5)P-2 phosphatases, OCRL-1 and UNC-26/synaptojanin, to prevent the build-up of PI(4,5)P-2 on endosomal membranes. In the absence of these four proteins, large amounts of PI(4,5)P-2 accumulate on endosomes, leading to embryonic lethality due to ectopic recruitment of proteins involved in actomyosin contractility. PDZD-8 localizes to the endoplasmic reticulum and regulates endosomal PI(4,5)P-2 levels via its lipid harboring SMP domain. Accumulation of PI(4,5)P-2 on endosomes is accompanied by impairment of their degradative capacity. Thus, cells use multiple redundant systems to maintain endosomal PI(4,5)P-2 homeostasis. Cellular membranes have distinct lipid compositions despite intermixing, and it is unclear why plasma membrane lipids do not accumulate on endosomes. Here, the authors use the C. elegans embryo to identify lipid transfer proteins and phosphatases that are critical for endosomal lipid homeostasis.
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