What makes worms grow and develop
Researchers of the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) in Dresden have discovered a new class of lipids which they named PEGC. They could show in nematodes that this lipid is involved in cholesterol transport and is unusually hydrophilic for lipids. The research team also describes the total de novo synthesis of the lipid together with colleagues at Dresden University of Technology.
The nematode Caenorhabditis elegans needs cholesterol for growth and survival under harsh conditions. In the absence of cholesterol, the worm’s development is stopped. The lab of Prof. Teymuras Kurzchalia at the MPI-CBG was looking for the hormone that can rescue this development arrest, but, to their surprise, researchers discovered a novel class of lipids that governs the development and growth of the organism. This new lipid has a sugar-like and polar head group, which clearly sets it apart from previously known lipids. „It is very hydrophilic, which is usually not the case with lipids,“ says Kurzchalia.
The researchers could show that this lipid plays a major role in regulating the cholesterol transport in cells and is therefore essential for a healthy development of nematodes. Defects in genes that control cholesterol transport can thus have serious consequences, as is the case in the Niemann-Pick disease type C: there’s a stoppage in the transport of cholesterol. Treating worms carrying mutations of genes associated with Niemann-Pick-C with the PEGC lipid could restore the trafficking. A next step will be to test the effect of the lipid on human cells from Niemann-Pick patients.
The new findings are the result of almost five years of work. Just synthesizing the lipid from scratch took one and a half years. "Others would have given up, our collaborator Hans-Joachim Knölker accepted the challenge," says Kurzchalia.
Sebastian Boland, Ulrike Schmidt, Vyacheslav Zagoriy, Julio L Sampaio, Raphael F Fritsche, Regina Czerwonka, Tilo Lübken, Jakob Reimann, Sider Penkov, Hans-Joachim Knölker & Teymuras V Kurzchalia:
Phosphorylated glycosphingolipids essential for cholesterol mobilization in Caenorhabditis elegans
Nature Chemical Biology, 3 April 2017 (Advance Online Publication)