Staff Members of the Institute of Biochemistry, TU - Institut für ...

characteristics of these two TAG synthases of the oleaginous yeast are currently under
investigation.
Is the function of Nte1p conserved from yeast to man?
Neuropathy target esterase (NTE) was originally identified as the target of
organophosphorous esters (OP) present in many pesticides as well as warfare agents.
Toxifications with OPs are causing delayed neuropathy in man and some other vertebrates.
The syndrome of the organophosphorous-induced delayed neuropathy (OPIDN) is
characterized by paralysis of the lower limbs and degeneration of long axons in the spinal
cord. These effects are common responses of neurons in metabolic disorders (e.g., diabetes),
toxic states and advanced age. Neither NTE nor its homologs in other organisms are closely
related to any other esterase or protease. The importance of NTE can be seen by the fact that
mice lacking this protein die as early embryos, and inactivation of SWS (swiss cheese), the
homolog of NTE in the fruit fly Drosophila melanogaster, leads to a progressive degeneration
of the nervous system, which can be observed as big “holes” in the brain of the fly.
Wild type, 21d sws, 8d
Figure 2: “Holes” in the brain of a sws-mutant of the fruit fly Drosophila melanogaster.
Heterologous expression of the murine NTE can completely substitute SWS in Drosophila,
demonstrating the functional conservation of this protein. A homolog of NTE is also present
in the yeast Saccharomyces cerevisiae encoded by NTE1. In contrast to higher eukaryotes,
deletion of this protein in the model organism yeast does not result in a phenotype under
several standard conditions tested. However, due to the presence of this polypeptide in a
single cell organism, NTE has to be involved in a more general context as in development,
neural survival and brain integrity. All efforts to identify the biological function, substrate,
and interaction partners of NTE in higher eukaryotes have failed so far. In contrast, Nte1p of
the yeast has been reported to exhibit phospholipase B activity, thus indicating a similar
function of the respective counterparts of higher eukaryotes. The question arises whether
Nte1p of Saccharomyces cerevisiae is a true member of the NTE protein family and thus
suitable as a model for unraveling the biological function of the NTE protein family. In vitro,
the functional conservation between NTE of higher eukaryotes and Nte1p of the yeast has
already been demonstrated. But is this also true in vivo? For answering this question, I
expressed NTE1 of the yeast heterologously in the fruit fly Drosophila melanogaster. A
functional compensation would be indicated by reversion of the phenotype of an sws mutant
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