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For 50 years, scientists have been looking for the identity of an enzyme (a protein), classified as an orphan because the gene that gives rise to that protein was unknown, and that participates in the final phase of the manufacture of plasminogens.
"Our contribution is that we have identified the gene that determines it and that for years has been elusive," says the principal investigator of this study, Montserrat Elías.
To achieve these findings, published in the journal Science, the Molecular Genetics Research Group of the University of Murcia (UMU) has used the Myxococcus xanthus bacteria as a model, because it is capable of synthesizing plasminogens as well as humans and animals.
The function of the gene, which to date was unknown to the scientific world, is considered the last missing link to complete the plasminogen biosynthesis chain: a class of very special phospholipids found almost exclusively in the cell membranes of the animals and that in the human being abound in the brain and the heart.
In common diseases, such as cancer or Alzheimer's disease, or other rare diseases, such as Zellweger's syndrome (cerebro-hepato-renal syndrome) or rhizomelic chondrodysplasia punctate, there are considerable changes in plasminogen levels.
In the case of Alzheimer's, for example, a very significant reduction is observed in the affected areas of the brain.
"In some cancers such as gastrointestinal there is an increase in these compounds and in others a decrease," explains the UMU researcher, who points out that for this reason it has been considered to use plasmogen as early markers of cancer.
The contributions of these UMU experts will allow to explore the direct relationship of plasmogen with various pathologies and, in addition, to reveal a very novel function of plasmogen: to allow a bacterium to see the light.
Together with Elías, the UMU researchers are Aránzazu Gallego, Antonio J. Monera, Elena Pajares, Eva Bastida, Ricardo Pérez, Antonio A. Iniesta and Marta Fontes.
In addition, he has co-directed the work Subramanian Padmanabhan, a researcher at the CSIC, with whom the group has been working closely for years.
A bacterium as a study model
The UMU team has been working with Myxococcus xanthus, a bacterium that lives in the soil for years.
According to the principal investigator, the effort to discover the role of a gene (called carF) that uses the bacteria to perceive light led them to identify the human gene.
"Analyzing possible human proteins we discovered that there was a protein (called TMEM189), of unknown function, which was very similar to the protein (CarF) of the bacteria and, therefore, we wondered if the human protein worked in the same way as the bacterial, "says Elías Arnanz.
To answer this question, the researchers replaced the bacterial (carF) gene with its equivalent gene in humans and several animals.
The result was "that the protein of humans and that of bacteria work identically, despite the enormous evolutionary distance between the two organisms," concludes Elías.
This equivalence between the two proteins will allow to quickly analyze, in the bacterium, the possible effect of the changes that are found in the future in the human gene.
Source: Universidad de Murcia
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