G protein β2 subunit interacts directly with neuropathy target esterase and regulates its activity

Neuropathy target esterase (NTE) was identified as the primary target of organophosphate compounds that cause a delayed neuropathy with degeneration of nerve axons. NTE is a novel phospholipase B anchored to the cytoplasmic face of endoplasmic reticulum and essential for embryonic and nervous development. However, little is known about the regulation of NTE. A human fetal brain cDNA library was screened for proteins that interact with NTE, G beta 2 and G beta 2-like I subunits were found to be able to bind the C-terminal of NTE in yeast. The interaction of GP2 and NTE was confirmed by in vivo co-immunoprecipitation analysis in COS7 cells. Furthermore, depletion of G beta 2 by RNA interference down regulated the activity of NTE but not its expression level. In addition, the activity of NTE was down regulated by the G protein signal pathway influencing factor, pertussis toxin, treatment in vivo. These findings suggest that G beta 2 may play a significant role in maintaining the activity of NTE. (c) 2006 Elsevier Ltd. All rights reserved.