The PCome of Caenorhabditis elegans as a prototypic model system for parasitic nematodes: identification of phosphorylcholine-substituted proteins.
The decoration of proteins and glycolipids with phosphorylcholine (PCho) has been shown in many organisms ranging from bacteria to multicellular parasites like nematodes. For bacteria this modifications is involved in invasion and persistence for pathogens. However, little is still known about the distribution of this modification on proteins, the precise epitope structures, and functions. In nematodes, the PCho-modification is widespread and at least on the glycosphingolipid level it represents a phylogenetic marker within the helminths. Nematode infections are still one of the most abundant diseases world-wide. Caenorhabditis elegans as the best characterized organism is an ideal model system for studying this type of protein modification and can therefore be regarded as a prototypic model system for parasitic nematodes. Interference with the PCho-decoration by targeting the glycosphingolipid biosynthesis and the choline metabolism has been shown to reduce nematode viability and fertility. Thus, the PCho-modification seems to play an additional important role for the development of nematodes. The development of drugs interfering with the PCho-substitution might, therefore, be a promising way for the development of new anthelminthic strategies. In this study we have analyzed the PCome of C. elegans to identify the PCho-modified proteins. Furthermore, we investigated the dynamics of this modification by analyzing the different developmental stages of this nematode. Our results demonstrate highly dynamic changes of this modification during development. Furthermore, we could show that this substitution can occur on proteins with large functional diversity and subcellular localization. We could further demonstrate that the PCho-modification greatly depends on proper N-glycosylation. However, there is clear indication that there might be a high structural diversity of the PCho-epitopes.
Grabitzki
Julia
J
Institute of Biochemistry, Faculty of Medicine, University of Giessen, Friedrichstrasse 24, Giessen, Germany.
Ahrend
Michael
M
Schachter
Harry
H
Geyer
Rudolf
R
Lochnit
Günter
G
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006031:Glycosylation; D008018:Life Cycle Stages; D008954:Models, Biological; D010449:Peptide Mapping; D010767:Phosphorylcholine / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D040901:Proteomics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D029742:Caenorhabditis elegans Proteins; D010767:Phosphorylcholine