Molecules of worldwide repute - The role of nitric oxide synthase in slime moulds

Vienna (FWF) - In 1992, it was awarded the title "Molecule of the Year". In 1998 three scientists received the Nobel Prize for their work on this molecule, which had already gained worldwide repute. And today, Georg Golderer from the Institute of Medical Chemistry and Biochemistry at Innsbruck University can report further groundbreaking findings. We are talking about nitric oxide (NO), a molecule performing a wide range of essential functions in animal organisms. Golderer and his team, sponsored by the Austrian Science Fund, have now detected this enzyme also in a single-celled non-animal organism, the slime mould Physarum polycephalum, and determined its biological role.

The slime mould can be cultured under laboratory conditions and represents a well established cell-biological model. It is thus ideally suited for the investigations pursued by Golderer, who followed two goals in his project. "Nitric oxide is a small gaseous molecule influencing many signal pathways within the cell. In animal organisms, for instance, it acts as a neurotransmitter, is involved in the regulation of the blood pressure and plays a diverse role in the immune response. While NO synthase activity was known to exist in non-animal organisms, it was, however, not accessible by any sequence data. Our first aim was therefore to identify NO synthase activity in the slime mould and to characterise the enzyme", says Golderer. "We were able to clean and clone the enzyme from the organism and thus characterise the first non-animal NO synthase".

Starring role in cell differentiation
Golderer also achieved his second aim, which was to shed new light on the biological function of NO synthase within the slime mould organism. "Upon entering a stage of hunger or desiccation, the slime mould is able to form spores and thus reproduce in time before its death. This process is called differentiation. We found out that a large amount of NO is produced during the hunger phase preceding differentiation", explains Golderer. The enzyme plays an essential part in controlling spore formation. It acts as a signal molecule triggering a whole series of reactions and finally controls the formation of fruiting bodies (spores). This reveals a new role of the NO signal pathway: the control in cell differentiation.

Regulatory details
The details of this process are not yet known, but Golderer intends to provide new findings in the coming years. "We now know the central significance of NO synthase in the slime mould. This is a fundamental progress. But we would also like to find out, for instance, with what proteins the molecule interacts, what reactions it triggers where in detail and what functions it performs", Golderer concludes. In this way, Golderer hopes to gain a better understanding of as yet unknown cellular control concepts of general biological relevance. The chemist considers this issue an important area of work for fundamental research.

Dr. Georg Golderer
University of Innsbruck, Institute of Medical Chemistry and Biochemistry
T +43 512 5073532

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August 29th, 2001