Molecular Biology of the Cell track citations

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

MBC in Press, published online ahead of print January 5, 2005
Mol. Biol. Cell 10.1091/mbc.E04-10-0874

A more recent version of this article appeared on March 1, 2005
This Article
Right arrow Full Text (PDF)
Right arrow Supplemental Material
Right arrow All Versions of this Article:
E04-10-0874v1
16/3/1120    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lagace, T. A.
Right arrow Articles by Ridgway, N. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lagace, T. A.
Right arrow Articles by Ridgway, N. D.

Submitted on October 7, 2004
Revised on December 2, 2004
Accepted on December 16, 2004

The Rate-limiting Enzyme in Phosphatidylcholine Synthesis Regulates Proliferation of the Nucleoplasmic Reticulum

Thomas A. Lagace* and Neale D. Ridgway{dagger}

Atlantic Research Center, Departments of Pediatrics, and Biochemistry and Molecular Biology, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4H7

Monitoring Editor: Jean Gruenberg

The nucleus contains a network of tubular invaginations of the nuclear envelope (NE), termed the nucleoplasmic reticulum (NR), implicated in transport, gene expression and calcium homeostasis. Here we show that proliferation of the NR, measured by the frequency of NE invaginations and tubules, is regulated by CTP:phosphocholine cytidylyltransferase-{alpha} (CCT{alpha}), the nuclear and rate-limiting enzyme in the CDP-choline pathway for phosphatidylcholine (PtdCho) synthesis. In chinese hamster ovary (CHO)-K1 cells, fatty acids triggered activation and translocation of CCT{alpha} to intranuclear tubules characteristic of the NR. This was accompanied by a twofold increase in NR tubules quantified by immunostaining for lamin A/C or the NE. CHO MT58 cells expressing a temperature-sensitive CCT{alpha} allele displayed reduced PtdCho synthesis and CCT{alpha} expression, and minimal proliferation of the NR in response to oleate compared with CHO MT58 cells stably expressing CCT{alpha}. Expression of CCT{alpha} mutants in CHO58 cells revealed that both enzyme activity and membrane binding promoted NR proliferation. In support of a direct role for membrane binding in NR tubule formation, recombinant CCT{alpha} caused the deformation of liposomes into tubules in vitro. This demonstrates that a key nuclear enzyme in PtdCho synthesis coordinates lipid synthesis and membrane deformation to promote formation of a dynamic nuclear-cytoplasmic interface.

*Present address: Dept of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390.

{dagger}Corresponding author. E-mail: nridgway{at}dal.ca




This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
G.-S. Han, L. O'Hara, G. M. Carman, and S. Siniossoglou
An Unconventional Diacylglycerol Kinase That Regulates Phospholipid Synthesis and Nuclear Membrane Growth
J. Biol. Chem., July 18, 2008; 283(29): 20433 - 20442.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
Z. Li and D. E. Vance
Thematic Review Series: Glycerolipids. Phosphatidylcholine and choline homeostasis
J. Lipid Res., June 1, 2008; 49(6): 1187 - 1194.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
K. Gehrig, R. B. Cornell, and N. D. Ridgway
Expansion of the Nucleoplasmic Reticulum Requires the Coordinated Activity of Lamins and CTP:Phosphocholine Cytidylyltransferase {alpha}
Mol. Biol. Cell, January 1, 2008; 19(1): 237 - 247.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. GenomicsHome page
Z. Yuan, A. Tie, M. Tarnopolsky, and M. Bakovic
Genomic organization, promoter activity, and expression of the human choline transporter-like protein 1
Physiol Genomics, September 14, 2006; 26(1): 76 - 90.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] --
Copyright © 2005 by The American Society for Cell Biology. Terms of copyright protection, warranties, and disclaimers.