Structure and conserved function of iso-branched sphingoid bases from the nematode Caenorhabditis elegans

Chemical Science
J Thomas HannichHoward Riezman

Abstract

Sphingolipids are bio-active metabolites that show structural diversity among eukaryotes. They are essential for growth of all eukaryotic cells but when produced in an uncontrolled manner can lead to cell death and pathologies including auto-immune reactions, cancer, diabetes and neurodegeneration. Caenorhabditis elegans is an important genetic model organism both to find new drug-targets against parasitic nematodes and to study the conserved roles of sphingolipids in animals like their essential functions in very basic cellular processes ranging from maintenance of cell polarity and mitochondrial repair to growth and survival. C. elegans produces sphingoid bases which are structurally distinct from those of other animals as both iso- and anteiso-branched species have been reported. Using metabolic labeling we show that most worm sphingoid bases are iso-branched. We have synthesized the nematode-specific C17 iso-branched sphinganine and its 1-deoxy analogue and could show that both the iso-branch and the 1-hydroxyl group are essential to form functional nematode sphingolipids which are needed to maintain intestinal function. The organism specificity was examined by complementation experiments in Saccharomyces cerevisiae yeast c...Continue Reading

References

Dec 15, 2000·Current Biology : CB·A LabrousseJ J Ewbank
Jul 15, 2003·Nature Biotechnology·Jeroen KrijgsveldAlbert J R Heck
Sep 18, 2003·Journal of Lipid Research·Henrik FyrstJulie D Saba
Apr 26, 2005·Bioorganic & Medicinal Chemistry·Jin-Wook KimYasuyuki Igarashi
Apr 9, 2008·The Journal of Biological Chemistry·Eugeni V EntchevTeymuras V Kurzchalia
May 24, 2008·Journal of Lipid Research·Sarah T PruettAlfred H Merrill
Apr 18, 2009·Science·Vincent MenuzJean-Claude Martinou
Jan 26, 2010·The Journal of Biological Chemistry·Anke PennoThorsten Hornemann
Apr 2, 2011·Cold Spring Harbor Perspectives in Biology·J Thomas HannichHoward Riezman
Aug 2, 2012·The Journal of Biological Chemistry·Richard JennemannHermann-Josef Gröne
May 27, 2014·Nature Methods·Gražvydas LukinavičiusKai Johnsson
Oct 4, 2014·Diabetes·Alaa OthmanThorsten Hornemann
Feb 27, 2015·Biological Chemistry·Xinzhu Deng, Richard Kolesnick
Mar 31, 2015·BMJ Open Diabetes Research & Care·Alaa OthmanThorsten Hornemann
May 8, 2015·The Journal of Biological Chemistry·Jingjing Duan, Alfred H Merrill
Nov 18, 2015·Scientific Reports·Suguru MurakamiKouichi Funato
Nov 28, 2015·ELife·Doris HöglingerCarsten Schultz
Mar 27, 2016·Neuropharmacology·Tanja GüntertOmolara O Ogunshola

❮ Previous
Next ❯

Citations

Jun 25, 2020·Proceedings of the National Academy of Sciences of the United States of America·Museer A LoneThorsten Hornemann
Jun 5, 2018·Natural Product Reports·Peter J HarrisonDominic J Campopiano
Feb 8, 2018·Nature Reviews. Molecular Cell Biology·Takeshi Harayama, Howard Riezman
Jul 23, 2020·Nature Metabolism·J Thomas HannichHoward Riezman
Feb 18, 2021·Metabolomics : Official Journal of the Metabolomic Society·Britta SpanierMichael Witting
Jun 3, 2021·International Journal of Molecular Sciences·Brianna M QuinvilleJagdeep S Walia
Oct 3, 2018·Langmuir : the ACS Journal of Surfaces and Colloids·Andreas Zumbuehl

❮ Previous
Next ❯

Methods Mentioned

BETA
gene knock-downs
light
electron microscopy
light microscopy
dissection

Software Mentioned

Matlab script
MetaXpress®
Fiji
ImageXpress®

Related Concepts

Related Feeds

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.

Cancer Metabolism

In order for cancer cells to maintain rapid, uncontrolled cell proliferation, they must acquire a source of energy. Cancer cells acquire metabolic energy from their surrounding environment and utilize the host cell nutrients to do so. Here is the latest research on cancer metabolism.