The rate-limiting enzyme in phosphatidylcholine synthesis is associated with nuclear speckles under stress conditions

Biochimica Et Biophysica Acta
Nicolás O FavaleNorma B Sterin-Speziale

Abstract

Phosphatidylcholine (PtdCho) is the most abundant phospholipid in eukaryotic membranes and its biosynthetic pathway is generally controlled by CTP:Phosphocholine Cytidylyltransferase (CCT), which is considered the rate-limiting enzyme. CCT is an amphitropic protein, whose enzymatic activity is commonly associated with endoplasmic reticulum (ER) translocation; however, most of the enzyme is intranuclearly located. Here we demonstrate that CCTα is concentrated in the nucleoplasm of MDCK cells. Confocal immunofluorescence revealed that extracellular hypertonicity shifted the diffuse intranuclear distribution of the enzyme to intranuclear domains in a foci pattern. One population of CCTα foci colocalised and interacted with lamin A/C speckles, which also contained the pre-mRNA processing factor SC-35, and was resistant to detergent and salt extraction. The lamin A/C silencing allowed us to visualise a second more labile population of CCTα foci that consisted of lamin A/C-independent foci non-resistant to extraction. We demonstrated that CCTα translocation is not restricted to its redistribution from the nucleus to the ER and that intranuclear redistribution must thus be considered. We suggest that the intranuclear organelle distrib...Continue Reading

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Mar 2, 2012·Journal of Biological Physics·Enrique Hernández-Lemus
Aug 21, 2012·World Journal of Biological Chemistry·Bryon EllisChunbin Zou
Oct 27, 2012·Biochimica Et Biophysica Acta·J P LayerenzaA Ves-Losada
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Feb 12, 2015·Journal of Lipid Research·Nicolás Octavio FavaleNorma Beatriz Sterin-Speziale
Nov 23, 2011·Biochemical Society Transactions·Ashraf N Malhas, David J Vaux
Jan 14, 2020·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Cecilia CasaliMaría C Fernández Tome

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