In the genome of an ordinary fruit fly, a research group in Leipzig has found three receptor genes of a kind nobody had recorded before, and one of them, ancient in its lineage, now bears the name mayo. Receptors of this family translate what arrives at the surface of a cell into a message the cell can act upon, and they shape a great many quiet processes in living bodies. What the Leipzig team has shown is that this small gene helps build the fly's intestine, and that the intestine, in turn, has some say over the rhythm of the heart. It is an early discovery, offering a window onto how organs
Leipzig Researchers Identify Adhesion GPCR 'mayo' as a Regulator of Intestinal Development in Fruit Flies
The gut and the heart, linked through a single receptor
In the genome of an ordinary fruit fly, a research group in Leipzig has found three receptor genes of a kind nobody had recorded before, and one of them, ancient in its lineage, now bears the name mayo. Receptors of this family translate what arrives at the surface of a cell into a message the cell can act upon, and they shape a great many quiet processes in living bodies. What the Leipzig team has shown is that this small gene helps build the fly's intestine, and that the intestine, in turn, has some say over the rhythm of the heart. It is an early discovery, offering a window onto how organs negotiate with one another, and whether the same conversation runs through human bodies remains a question the study has only raised.
In the genome of the fruit fly, a team at Leipzig University has identified three adhesion GPCR genes that had never been catalogued. One of them, evolutionarily old, they named mayo. Their new study shows what that gene does inside a living animal, and the answer stretches from the gut all the way to the heart.
Adhesion GPCRs are part of a large family of receptors that carry signals from the outside of a cell to its interior. Humans have around 700 variants, and they help govern senses, hormones and cardiovascular control. The researchers at the Rudolf Schönheimer Institute of Biochemistry chose the fruit fly as their model, since roughly 75 per cent of the genes involved in human disease have counterparts in the fly.
When the team switched off mayo, the flies developed elongated guts. Dr Beatriz Blanco-Redondo, the corresponding author, explained that mayo guides the formation of the midgut by encouraging the growth of enterocytes, the cells lining the intestine. The effect did not stop there. Flies lacking mayo in the intestine showed faster heart rates and dangerous palpitations, which the researchers attribute to disrupted ion uptake and the systemic potassium balance that enterocytes help regulate.
A similar pattern appeared in mice, where a different adhesion GPCR produced an enlarged intestine, suggesting these receptors may play a role in gut construction across species. The authors are careful to present any relevance to humans as a possibility rather than a finding.
Professor Tobias Langenhan, who leads General Biochemistry at the institute, describes the project as only beginning. The next step is to identify the signaling pathway in which mayo operates, a discovery that would reveal how the receptor steers intestinal development and where future answers may lie.
In the genome of the fruit fly, a team at Leipzig University has found three adhesion GPCR genes that nobody had catalogued before. One of them, very old in evolutionary terms, they named mayo. Their latest publication shows what that gene does in a living animal, and the answer reaches from the gut to the heart.
Some background helps here. Adhesion GPCRs belong to the large family of G protein-coupled receptors, which take a stimulus arriving at the outside of a cell and turn it into a biochemical signal inside. Humans have about 700 variants of these receptors. They are responsible for sensory impressions, hormonal cycles and control of the cardiovascular system, among other jobs.
The work was done at the Rudolf Schönheimer Institute of Biochemistry in the Faculty of Medicine. The fruit fly, Drosophila, was the model. Researchers in the field use it because it is genetically close to humans: scientists estimate that around 75 per cent of the genes involved in human disease are also found in the fly.
The team studied animals in which the mayo gene had been switched off. These knockout flies developed elongated guts. According to Dr Beatriz Blanco-Redondo, corresponding author of the study, mayo shapes the development of the midgut by promoting the growth of enterocytes, the epithelial cells of the intestinal lining.
The effect did not stay in the gut. When mayo was lost in the intestine, the flies' heart rate sped up and they developed dangerous palpitations. The researchers read this as a sign that intestine and heart are connected through mayo's role in enterocyte proliferation. Enterocytes regulate ion uptake, and through it systemic potassium levels and, secondarily, heart rate.
There is a parallel in mammals. Overexpressing a different adhesion GPCR in mouse intestinal cells produced a similar picture, a mega-intestine. From this the authors conclude that adhesion GPCRs take part in building the gastrointestinal tract in other species as well, and that these phenomena may be relevant in humans. That last point is a possibility the study raises, not something it has shown.
Professor Tobias Langenhan, who holds the chair of General Biochemistry at the institute and is also a corresponding author, describes the project as just beginning. The main goal now is to identify the signaling pathway in which mayo operates, so the team can learn how the receptor controls intestinal development. That pathway is the thing to watch for in later results.
Citazioni salienti
mayo affects midgut development in Drosophila by promoting the growth of enterocytes, the epithelial cells of the intestinal mucosa.— Dr Beatriz Blanco-Redondo, corresponding author
The research is at its beginning; the main goal is to identify the signaling pathway in which mayo is involved.— Prof. Tobias Langenhan, Rudolf Schönheimer Institute
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