@article{f7e4df6695474780b71b6b0245a1fa19,
title = "Apicobasal domain identities of expanding tubular membranes depend on glycosphingolipid biosynthesis",
abstract = "Metazoan internal organs are assembled from polarized tubular epithelia that must set aside an apical membrane domain as a lumenal surface. In a global Caenorhabditis elegans tubulogenesis screen, interference with several distinct fatty-acid-biosynthetic enzymes transformed a contiguous central intestinal lumen into multiple ectopic lumens. We show that multiple-lumen formation is caused by apicobasal polarity conversion, and demonstrate that in situ modulation of lipid biosynthesis is sufficient to reversibly switch apical domain identities on growing membranes of single post-mitotic cells, shifting lumen positions. Follow-on targeted lipid-biosynthesis pathway screens and functional genetic assays were designed to identify a putative single causative lipid species. They demonstrate that fatty-acid biosynthesis affects polarity through sphingolipid synthesis, and reveal ceramide glucosyltransferases (CGTs) as end-point biosynthetic enzymes in this pathway. Our findings identify glycosphingolipids, CGT products and obligate membrane lipids, as critical determinants of in vivo polarity and indicate that they sort new components to the expanding apical membrane.",
author = "Hongjie Zhang and Nessy Abraham and Khan, {Liakot A.} and Hall, {David H.} and Fleming, {John T.} and Verena G{\"o}bel",
note = "Funding Information: Strains and plasmids were provided by D. Baillie (Fraser University, Burnaby, British Columbia, Canada), A. Croce (IFOM Istituto FIRC di Oncologia Molecolare, Milan, Italy), B. Grant (Rutgers University, Piscataway, New Jersey, USA), K. Kemphues (Cornell University, Ithaca, New York, USA), K. Nehrke (University of Rochester Medical Center, Rochester New York, USA), G. Ruvkun (Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA), K. Strange (Vanderbilt University Medical Center, Salisbury Cove Maine, USA), J. Simske (Case Western Reserve University School of Medicine, Cleveland, Ohio, USA), S. Mitani (National Bioresource Project Japan) and the Caenorhabditis Genetics Center (NIH Center for Research Resources). We thank G. Ruvkun for the lethal RNAi library, and J. Moore (Avanti Polar Lipids); Mary McKee (MGH Microscopy Core/partially funded by the IBD grant DK43351 and BA DE award DK57521) and K. Nygen; Christopher Crocker; and Edward Membreno for contributions to LC/MS; TEM; illustrations and C. elegans maintenance, respectively. We thank F. Solomon and B. Winckler for critical reading of the manuscript and H. Weinstein and A. Walker for ongoing support. This work was supported by NIH grants HD044589 and GM078653 and a Mattina R. Proctor Award to V.G.",
year = "2011",
month = oct,
doi = "10.1038/ncb2328",
language = "English (US)",
volume = "13",
pages = "1189--1201",
journal = "Nature Cell Biology",
issn = "1465-7392",
publisher = "Nature Publishing Group",
number = "10",
}