RRC ID 46549
Author Zhang H, Abraham N, Khan LA, Hall DH, Fleming JT, Göbel V.
Title Apicobasal domain identities of expanding tubular membranes depend on glycosphingolipid biosynthesis.
Journal Nat Cell Biol
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.
Volume 13(10)
Pages 1189-201
Published 2011-9-18
DOI 10.1038/ncb2328
PII ncb2328
PMID 21926990
PMC PMC3249144
MeSH Acetyl-CoA Carboxylase / genetics Acetyl-CoA Carboxylase / metabolism Alcohol Oxidoreductases / genetics Alcohol Oxidoreductases / metabolism Animals Caenorhabditis elegans / enzymology Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans / ultrastructure Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Cell Enlargement Cell Membrane / enzymology Cell Membrane / metabolism* Cell Membrane / ultrastructure Cell Polarity* / genetics Coenzyme A Ligases / genetics Coenzyme A Ligases / metabolism Epithelial Cells / enzymology Epithelial Cells / metabolism* Epithelial Cells / ultrastructure Genotype Glucosyltransferases / genetics Glucosyltransferases / metabolism Glycosphingolipids / biosynthesis* Hydroxylation Intestinal Mucosa / enzymology Intestinal Mucosa / metabolism* Intestinal Mucosa / ultrastructure Microscopy, Confocal Microscopy, Fluorescence Phenotype RNA Interference Serine C-Palmitoyltransferase / genetics Serine C-Palmitoyltransferase / metabolism Time Factors Transport Vesicles / metabolism
IF 17.728
Times Cited 70
C.elegans tm999 tm504 tm1425