Muhlig-Versen, M and da Cruz, AB and Tschape, JA and Moser, M and Buttner, R and Athenstaedt, K and Glynn, P and Kretzschmar, D (2005) Loss of Swiss cheese/neuropathy target esterase activity causes disruption of phosphatidylcholine homeostasis and neuronal and glial death in adult Drosophila. JOURNAL OF NEUROSCIENCE, 25 (11). pp. 2865-2873. ISSN 0270-6474,
Full text not available from this repository. (Request a copy)Abstract
The Drosophila Swiss cheese (sws) mutant is characterized by progressive degeneration of the adult nervous system, glial hyperwrapping, and neuronal apoptosis. The Swiss cheese protein (SWS) shares 39% sequence identity with human neuropathy target esterase (NTE), and a brain-specific deletion of SWS/NTE in mice causes a similar pattern of progressive neuronal degeneration. NTE reacts with organophosphate compounds that cause a paralyzing axonal degeneration in humans and has been shown to degrade endoplasmic reticulum-associated phosphatidylcholine (PtdCho) in cultured mammalian cells. However, its function within the nervous system has remained unknown. Here, we show that both the fly and mouse SWS proteins can rescue the defects that arise in sws mutant flies, whereas a point mutation in the proposed active site cannot restore SWS function. Overexpression of catalytically active SWS caused formation of abnormal intracellular membraneous structures and cell death. Cell-specific expression revealed that not only neurons but also glia depend autonomously on SWS. In wild-type flies, endogenous SWS was detected by immunohistochemistry in the endoplasmic reticulum (the primary site of PtdCho processing) of neurons and in some glia. sws mutant flies lacked NTE-like esterase activity and had increased levels of PtdCho. Conversely, overexpression of SWS resulted in increased esterase activity and reduced PtdCho. We conclude that SWS is essential for membrane lipid homeostasis and cell survival in both neurons and glia of the adult Drosophila brain and that NTE may play an analogous role in vertebrates.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | LECITHIN-CHOLESTEROL ACYLTRANSFERASE; INDUCED DELAYED NEUROPATHY; LAMINA GANGLIONARIS; BRAIN; NEURODEGENERATION; APOPTOSIS; CELLS; DOMAIN; ORGANOPHOSPHATES; POLYNEUROPATHY; Drosophila; NTE; neurodegeneration; organophosphate-induced delayed neuropathy; phospholipids; ER |
| Subjects: | 500 Science > 590 Zoological sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Zoologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 May 2021 13:26 |
| Last Modified: | 20 May 2021 13:26 |
| URI: | https://pred.uni-regensburg.de/id/eprint/36364 |
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