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Published online 4 October 2004. doi:10.1083/jcb.200406136
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 167, Number 1, 35-41
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XBP1 : a link between the unfolded protein response, lipid biosynthesis, and biogenesis of the endoplasmic reticulum



Rungtawan Sriburi1, Suzanne Jackowski2, Kazutoshi Mori3, and Joseph W. Brewer1

1 Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153
2 Protein Science Division, Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105
3 Department of Biophysics, Graduate School of Science, Kyoto University, Kyoto 606-8502, Japan

Correspondence to Joseph W. Brewer: jbrewer{at}lumc.edu


Abstract
When the protein folding capacity of the endoplasmic reticulum (ER) is challenged, the unfolded protein response (UPR) maintains ER homeostasis by regulating protein synthesis and enhancing expression of resident ER proteins that facilitate protein maturation and degradation. Here, we report that enforced expression of XBP1(S), the active form of the XBP1 transcription factor generated by UPR-mediated splicing of XBP1 mRNA, is sufficient to induce synthesis of phosphatidylcholine, the primary phospholipid of the ER membrane. Cells overexpressing XBP1(S) exhibit elevated levels of membrane phospholipids, increased surface area and volume of rough ER, and enhanced activity of the cytidine diphosphocholine pathway of phosphatidylcholine biosynthesis. These data suggest that XBP1(S) links the mammalian UPR to phospholipid biosynthesis and ER biogenesis.

Abbreviations used in this paper: ATF, activating transcription factor; BiP, binding protein; CCT, choline cytidylyltransferase; CDP-choline, cytidine diphosphocholine; CEPT, choline/ethanolaminephosphotransferase; CK, choline kinase; CPT, cholinephosphotransferase; PtdCho, phosphatidylcholine; PtdEtn, phosphatidylethanolamine; UPR, unfolded protein response; XBP1, X-box binding protein 1; XBP1(S), XBP1 (spliced); XBP1(U), XBP1(unspliced).


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