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

Developmental Cell
Afreen HaiderDavid B Savage

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.

Citations

Aug 18, 2018·Journal of Lipid Research·Jonghwa Lee, Neale D Ridgway
Jul 2, 2019·Chemical Communications : Chem Comm·Yawei DuXinsong Li
Nov 24, 2019·International Journal of Molecular Sciences·Lior PytowskiDavid J Vaux
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Methods Mentioned

BETA
transgenic
transmission electron microscopy
confocal microscopy
acylation
phosphotransferase
phosphotransferase 1
PCR
Fluorescence microscopy
transfection
dissection

Key Resources (RRID) Mentioned

CVCL_KB57
CVCL_0123
CVCL_Z232
IMSR_JAX
MGI

Software Mentioned

Leica LAS AF Lite
cNLS mapper
Adobe Photoshop
pClamp
GraphPad Prism
IMARIS
ImageJ

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