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

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.

journal_name

Dev Cell

journal_title

Developmental cell

authors

Haider A,Wei YC,Lim K,Barbosa AD,Liu CH,Weber U,Mlodzik M,Oras K,Collier S,Hussain MM,Dong L,Patel S,Alvarez-Guaita A,Saudek V,Jenkins BJ,Koulman A,Dymond MK,Hardie RC,Siniossoglou S,Savage DB

doi

10.1016/j.devcel.2018.04.012

subject

Has Abstract

pub_date

2018-05-21 00:00:00

pages

481-495.e8

issue

4

eissn

1534-5807

issn

1878-1551

pii

S1534-5807(18)30287-9

journal_volume

45

pub_type

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