Dec 9, 2008

Degradation of neuropathy target esterase by the macroautophagic lysosomal pathway

Life Sciences
Ding-Xin LongYi-Jun Wu

Abstract

Neuropathy target esterase (NTE) was proposed as the initial target during the process of organophosphate-induced delayed neuropathy (OPIDN) in humans and some sensitive animals. NTE was recently identified as a novel phospholipase B that is anchored to the cytoplasmic side of the endoplasmic reticulum. However, little is known about the degradation of NTE. In this study, we have investigated the role of the macroautophagic-lysosomal pathway in NTE degradation in neuronal and non-neuronal cells. Macroautophagy inhibitors and activators were used to interrupt the lysosomal pathway, and NTE protein level was followed using western blotting analysis. A fluorescent microscopy assay was used to determine the co-localization of NTE and lysosomes. Western blotting analysis showed that the macroautophagy inhibitors 3-methyladenine and ammonium chloride increased the levels of a heterologously expressed NTE-GFP fusion protein as well as endogenous NTE. Starvation had the opposite effect. The role of macroautophagy in NTE degradation was further supported by the co-localization of exogenous NTE with lysosomes in starved COS7 cells. Furthermore, the contribution of NTE activity and protein domains to the degradation of NTE by macroautopha...Continue Reading

  • References27
  • Citations5

References

Mentioned in this Paper

Establishment and Maintenance of Localization
Buffers
Biochemical Pathway
Lysosome Assembly Pathway
NTE, lymphocyte neuropathy target esterase
Transfection
Abnormal Degeneration
Molecular Helix
Western Blotting
Protoplasm

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