1. PCYT1A Regulates Phosphatidylcholine Homeostasis from the Inner Nuclear Membrane in Response to Membrane Stored Curvature Elastic Stress
- Author
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Haider, Afreen, Wei, Yu-Chen, Lim, Koini, Barbosa, Antonio D, Liu, Che-Hsiung, Weber, Ursula, Mlodzik, Marek, Oras, Kadri, Collier, Simon, Hussain, M Mahmood, Dong, Liang, Patel, Satish, Alvarez-Guaita, Anna, Saudek, Vladimir, Jenkins, Benjamin J, Koulman, Albert, Dymond, Marcus K, Hardie, Roger C, Siniossoglou, Symeon, Savage, David B, Koulman, Albert [0000-0001-9998-051X], Hardie, Roger [0000-0001-5531-3264], Savage, David [0000-0002-7857-7032], and Apollo - University of Cambridge Repository
- Subjects
Cell Nucleus ,Male ,Nuclear Envelope ,Cell Membrane ,Saccharomyces cerevisiae ,Models, Biological ,Article ,Elasticity ,CCT ,Mice, Inbred C57BL ,Mice ,stored curvature elastic stress ,Drosophila melanogaster ,PCYT1A ,Stress, Physiological ,Kennedy pathway ,Phosphatidylcholines ,lipidomics ,Animals ,Homeostasis ,Choline-Phosphate Cytidylyltransferase ,phosphatidylcholine ,Phospholipids - Abstract
Summary Cell and organelle membranes consist of a complex mixture of phospholipids (PLs) that determine their size, shape, and function. Phosphatidylcholine (PC) is the most abundant phospholipid in eukaryotic membranes, yet how cells sense and regulate its levels in vivo remains unclear. Here we show that PCYT1A, the rate-limiting enzyme of PC synthesis, is intranuclear and re-locates to the nuclear membrane in response to the need for membrane PL synthesis in yeast, fly, and mammalian cells. By aligning imaging with lipidomic analysis and data-driven modeling, we demonstrate that yeast PCYT1A membrane association correlates with membrane stored curvature elastic stress estimates. Furthermore, this process occurs inside the nucleus, although nuclear localization signal mutants can compensate for the loss of endogenous PCYT1A in yeast and in fly photoreceptors. These data suggest an ancient mechanism by which nucleoplasmic PCYT1A senses surface PL packing defects on the inner nuclear membrane to control PC homeostasis., Graphical Abstract, Highlights • PCYT1A catalyzes the rate-limiting reaction in phosphatidylcholine (PC) synthesis • PC deficiency increases membrane lipid stored curvature elastic (SCE) stress • PCYT1A uses a nascent amphipathic helix to sense SCE in the nuclear membrane • PCYT1A mutants lacking a nuclear localization signal rescue PCYT1A-deficient cells, Phosphatidylcholine (PC) is the major constituent of cellular membranes. Haider et al. show that PCYT1A, the rate-limiting enzyme of PC synthesis, translocates onto the inner nuclear membrane in response to increased PC need in yeast, fly, and mammalian cells. This PCYT1A re-localization is governed by membrane stored curvature elastic stress.
- Published
- 2018
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