Research paper reveals effects of enzyme loss


Dr. Doris Kretzschmar
Dr. Doris Kretzschmar

Glial expression of Swiss-cheese (SWS), the Drosophila orthologue of Neuropathy Target Esterase, is required for neuronal ensheathment and function, by Dutta S, Rieche F, Eckl N, Duch C, and Kretzschmar D.

That’s the title of a paper, recently published, that describes work originating from the laboratory of Doris Kretzschmar. In this work, Dr. Kretzschmar and postdoctoral fellow Sudeshna Dutta created a genetic mutation in a fruit fly enzyme that is analogous to neuropathy target esterase (NTE), an enzyme posessed by humans.

For years it has been known that certain chemicals, called organophosphates (OPs), inhibit the function of NTE, and that NTE inhibition might be the link to a disease of motor nerves caused by OPs. OPs are used as insecticides and have a variety of other uses in industry. During alcohol prohibition, an OP contaminant in a bootleg product known as Ginger Jake caused toxic injuries marked by a peculiar gait called “Jake Leg” – this was the first clue that NTE might be important to nerve development and function.

Now, with the mutant fruit flies, we can more closely study the molecular mechanisms by which changes in this protein (called SWS, or Swiss Cheese, in flies) causes neuronal damage and movement defects. Mutations in humans cause ataxia (the loss of full control of bodily movements), spastic paraplegia (stiffness and contraction in the lower limbs), and paralysis, as well as other symptoms like blindness and mental retardation. With a better understanding of SWS (and NTE), we may someday be able to provide treatment to those with mutations of NTE or injuries from exposure to OP chemicals.

Here are some movies that show the effect of deleting the SWS gene in flies: Dutta et al movie wild type vs Dutta et al movie knockdown. It makes their movement uncoordinated and they have problems walking, whereas the wild type (WT) walks straight up their containment vials.