Neuroscience and plant biology team up to explore endocytosis

1 October 2016
Some research projects apply more than just one model organism. As many basic cell processes are quite similar across lifeforms, the exact effects of molecules can be compared in different organisms. One example is the multidisciplinary research carried out by the labs of Patrik Verstreken (VIB-KU Leuven) and Jenny Russinova (VIB-UGent). In plants, fruit flies and human cells, they discovered the mechanisms by which inhibitors of endocytosis disrupt energy metabolism.

When molecules (such as proteins) come near a cell, they can be engulfed by it. This process is called endocytosis. The paper, published in Nature Communications, unveiled the actual biological consequences of ES9, a molecule that inhibits endocytosis. By comparing the effects on plants (Arabidopsis), fruit flies (Drosophila), and human cells, the team showed that differences in cell physiology systems may require the development of plant-specific or animal-specific inhibitors for medical uses.

Patrik, your neuroscience lab joined hands with Jenny’s plant biology lab. What was the driver behind this collaboration?
Patrik: “We are both interested in how cells communicate with each other. Some of these mechanisms, such as endocytosis, are quite similar. When Jenny’s lab began isolating inhibitors of the process, we were obviously interested in assessing whether the compounds that are active in plants also affect flies. The findings also tell us that apparent plant-specific compounds or insect-specific compounds may have to be treated with care, as these tools may have more far-reaching
effects than originally assumed.”

Jenny, what important lesson do you take from this research?
Jenny: “Plant researchers sometimes use small molecules discovered in the mammalian field, assuming they have the same mode of action. But although biological processes can be very similar,
the differences in cell physiology can cause varying results. For example, we observed that ES9 and the known drug TyrA23 cause acidification of the plants’ cytoplasm, thereby inhibiting endocytosis.
Because extracellular spaces in plants and mammals have an opposite pH, such drugs will affect cytoplasmic pH differently. This means we have to use compounds with the greatest caution and
carefully attune them to the right organisms.”

Let’s also ask some other contributors about the project. Wim, what about next steps and plans moving forward?
Wim Dejonghe: “Our findings open pathways to develop ES9 through chemical processes into a specific plant endocytosis inhibitor. We’re also looking forward to further studying the effects of extracellular pH on plant receptor activation and internalization.”

And finally: Sabine, what struck you the most about the outcomes of this research?
Sabine Kuenen: “Not only did ES9 treatment in drosophila larvae result in endocytic phenotypes, resembling mutants that we had studied before in the lab, also mitochondrial function was severely affected, pointing out that additional effects can be induced when using inhibitors, especially when using them in different model organisms.”

Dejonghe et al., Nature Communications 2016

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