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Apicobasal domain identities of expanding tubular membranes depend on glycosphingolipid biosynthesis
Zhang H.1; Abraham N.1; Khan L.A.1; Hall D.H.2; Fleming J.T.1; Gobel V.1
2011-10-01
Source PublicationNature Cell Biology
ISSN14657392 14764679
Volume13Issue:10Pages:1189-1201
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. © 2011 Macmillan Publishers Limited. All rights reserved.

DOI10.1038/ncb2328
URLView the original
Indexed BySCI
Language英语
WOS Research AreaCell Biology
WOS SubjectCell Biology
WOS IDWOS:000295617900009
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Cited Times [WOS]:68   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Affiliation1.Massachusetts General Hospital
2.Albert Einstein College of Medicine of Yeshiva University
Recommended Citation
GB/T 7714
Zhang H.,Abraham N.,Khan L.A.,et al. Apicobasal domain identities of expanding tubular membranes depend on glycosphingolipid biosynthesis[J]. Nature Cell Biology,2011,13(10):1189-1201.
APA Zhang H.,Abraham N.,Khan L.A.,Hall D.H.,Fleming J.T.,&Gobel V..(2011).Apicobasal domain identities of expanding tubular membranes depend on glycosphingolipid biosynthesis.Nature Cell Biology,13(10),1189-1201.
MLA Zhang H.,et al."Apicobasal domain identities of expanding tubular membranes depend on glycosphingolipid biosynthesis".Nature Cell Biology 13.10(2011):1189-1201.
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