Apicobasal domain identities of expanding tubular membranes depend on glycosphingolipid biosynthesis

Hongjie Zhang, Nessy Abraham, Liakot A. Khan, David H. Hall, John T. Fleming, Verena Göbel

Research output: Contribution to journalArticle

65 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1189-1201
Number of pages13
JournalNature Cell Biology
Volume13
Issue number10
DOIs
StatePublished - Oct 2011

Fingerprint

ceramide glucosyltransferase
Glycosphingolipids
Lipids
Membranes
Fatty Acids
Sphingolipids
Caenorhabditis elegans
Enzymes
Membrane Lipids
Epithelium

ASJC Scopus subject areas

  • Cell Biology

Cite this

Apicobasal domain identities of expanding tubular membranes depend on glycosphingolipid biosynthesis. / Zhang, Hongjie; Abraham, Nessy; Khan, Liakot A.; Hall, David H.; Fleming, John T.; Göbel, Verena.

In: Nature Cell Biology, Vol. 13, No. 10, 10.2011, p. 1189-1201.

Research output: Contribution to journalArticle

Zhang, Hongjie ; Abraham, Nessy ; Khan, Liakot A. ; Hall, David H. ; Fleming, John T. ; Göbel, Verena. / Apicobasal domain identities of expanding tubular membranes depend on glycosphingolipid biosynthesis. In: Nature Cell Biology. 2011 ; Vol. 13, No. 10. pp. 1189-1201.
@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",
year = "2011",
month = "10",
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",

}

TY - JOUR

T1 - Apicobasal domain identities of expanding tubular membranes depend on glycosphingolipid biosynthesis

AU - Zhang, Hongjie

AU - Abraham, Nessy

AU - Khan, Liakot A.

AU - Hall, David H.

AU - Fleming, John T.

AU - Göbel, Verena

PY - 2011/10

Y1 - 2011/10

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=80053562290&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80053562290&partnerID=8YFLogxK

U2 - 10.1038/ncb2328

DO - 10.1038/ncb2328

M3 - Article

VL - 13

SP - 1189

EP - 1201

JO - Nature Cell Biology

JF - Nature Cell Biology

SN - 1465-7392

IS - 10

ER -