Research Story: Dr. Hongjie Zhang’s recent publication in Nature Cell Biology

Nov - 15
2011

Research Story: Dr. Hongjie Zhang’s recent publication in Nature Cell Biology

Many congratulations to Dr. Hongjie Zhang for her tremendous research work for the past years and a recent publication in Nature Cell Biology (article) in September 20111.

Hongjie is an Instructor in Pediatrics in Department of Pediatrics at Massachusetts General Hospital. Her article at Nature Cell Biology is entitled as “Apicobasal domain identities of expanding tubular membranes depend on glycosphingolipid biosynthesis” (PMID: 21926990)1. In this paper, Hongjie and colleagues investigated the potential roles of sphingolipids on epithelial polarity in Caenorhabditis elegans. They found that glycosphingolipids mediate apical sorting, and specifically help maintain apicobasal polarity in Caenorhabditis elegans. The abstract of their article is described here. 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 membrane1.

Hyenne, V and Labouesse, M enthusiastically commented their article2 as “fascinating” and this “unbiased genetic study provides compelling support for the insightful model proposed more than 20 years ago for the potential role of sphingolipids in epithelial polarity. It opens new avenues of research, as the powerful genetic C. elegans system should be instrumental to determine at which level GSLs act and how they might interact with classical polarity complexes along with phosphoinositides2”.

Anyone interested in the study is welcome to contact Dr. Zhang with the following contact information.
Dr. Hongjie Zhang
Massachusetts General Hospital
Mucosal Immunology Laboratory, Rm 3103
114 16th Street, Charlestown, MA 02129
Phone (617)726-4171
Email: hzhang14@partners.org
Cheers

HMS-CSSA

1. Zhang, H. et al. Apicobasal domain identities of expanding tubular membranes depend on glycosphingolipid biosynthesis. Nat Cell Biol 13, 1189-201 (2011). Zhang NCB Article
2. Hyenne, V. & Labouesse, M. Making sense of glycosphingolipids in epithelial polarity. Nat Cell Biol 13, 1185-7 (2011).