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PCYT1A Regulates Phosphatidylcholine Homeostasis from the Inner Nuclear Membrane in Response to Membrane Stored Curvature Elastic Stress.

Published version
Peer-reviewed

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Authors

Haider, Afreen 
Wei, Yu-Chen 
Lim, Koini 
Barbosa, Antonio D 
Liu, Che-Hsiung 

Abstract

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.

Description

Keywords

CCT, Kennedy pathway, PCYT1A, lipidomics, phosphatidylcholine, stored curvature elastic stress, Animals, Cell Membrane, Cell Nucleus, Choline-Phosphate Cytidylyltransferase, Drosophila melanogaster, Elasticity, Homeostasis, Male, Mice, Mice, Inbred C57BL, Models, Biological, Nuclear Envelope, Phosphatidylcholines, Saccharomyces cerevisiae, Stress, Physiological

Journal Title

Dev Cell

Conference Name

Journal ISSN

1534-5807
1878-1551

Volume Title

45

Publisher

Elsevier BV
Sponsorship
Wellcome Trust (100574/Z/12/Z)
Wellcome Trust (107064/Z/15/Z)
Biotechnology and Biological Sciences Research Council (BB/M007006/1)
Medical Research Council (MC_UU_12012/5)
Wellcome Trust (100140/Z/12/Z)
Wellcome Trust (108042/Z/15/Z)
Wellcome Trust (093026/Z/10/Z)
Medical Research Council (MC_PC_12012)