Flies Without Grandchildren

Childless dynasties are used as name givers for a group of genes and their encoded proteins. Like these royal lines that became extinct, fruit flies mutated in these proteins remain without second generation offspring. Scientists of the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) have discovered a new protein in this group, named Capsuléen, which is necessary for the formation of germ cells in Drosophila. They have elucidated a number of details of how this protein contributes to preserving the line.

Living things consist of a multitude of different proteins - more than are found in the form of blueprints in the genetic material. Behind this there are strategies used by living things to change proteins; thus, they make more of what they have at their disposal. The proteins in the organism regulate processes such as the transmission of signals, the packaging of the genetic material or the transport of molecules.

Methyltransferases are among the ‘decorators’ in the cell. These proteins attach hydrocarbons, called methyl groups, to other proteins. The resulting pattern of modification determines, for example, the molecular interaction with partner proteins and also whether it is active at all. Errors in methylation can have serious consequences: They can make proteins non-functional and are associated with cancer.

Scientists under the leadership of Professor Bernard Mechler, head of the Division of Developmental Genetics at the German Cancer Research Center, have discovered an interesting function of the methyltransferase Capsuléen, which is essential for the fertility of fruit flies. The researchers had noticed that flies that do not have two functional gene copies of Capsuléen remain without second generation offspring, because their immediate offspring produce no germ cells. Further experiments revealed that the nurse cells feeding the Drosophila egg with all that it needs lack an important detail in the genetically modified flies: they miss a cellular structure called ‘nuage’ that forms a nebulous ring around the nucleus of the nurse cells and has been termed with the French word for ‘cloud’. Specific proteins that are required for the formation of the germ cells, such as the protein Tudor, are missing in the nuage of the affected animals.

One could believe that the loss of Tudor is caused by the defective regulation of a target protein that is methylated by Capsuléen. The scientists discovered such target proteins, but proved that the absence of methylation of these proteins has nothing to do with the distribution of Tudor. “Thus we were able to separate the two biological processes from each other,” says Joël Anne of the Developmental Genetics Division. However, Capsuléen does not act on its own, as Anne further explains. It binds to another protein named after the extinct French dynasty of Valois. At present the researchers are searching for the other important component that would explain, from a molecular perspective, how the infertility of the flies is brought about. Anne is convinced that there is at least one more molecule involved whose loss also leads to flies without grandchildren.

Joël Anne, Roger Ollo, Anne Ephrussi, and Bernard M. Mechler
Arginine methyltransferase Capsuléen is essential for methylation of spliceosomal Sm proteins and germ cell formation in Drosophila, Development (2006)
doi: 02687.

The task of the Deutsches Krebsforschungszentrum in Heidelberg (German Cancer Research Center, DKFZ) is to systematically investigate the mechanisms of cancer development and to identify cancer risk factors. The results of this basic research are expected to lead to new approaches in the prevention, diagnosis and treatment of cancer. The Center is financed to 90 percent by the Federal Ministry of Education and Research and to 10 percent by the State of Baden-Wuerttemberg. It is a member of the Helmholtz Association of National Research Centers (Helmholtz-Gemeinschaft Deutscher Forschungszentren e.V., HGF).

dkfz.de/en/abteilungen/fspa/a040.html

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