Table of Contents
ISRN Anesthesiology
Volume 2012 (2012), Article ID 970795, 7 pages
http://dx.doi.org/10.5402/2012/970795
Research Article

Isoflurane Enhances the Moonlighting Activity of GAPDH: Implications for GABAA Receptor Trafficking

1Department of Anesthesiology, University of Missouri-Kansas City/Saint Luke’s Hospital, 4401 Wornall Road, Kansas City, MO 64111, USA
2Department of Biochemistry, Kansas City University of Medicine and Biosciences, 1750 Independence Avenue, Kansas City, MO 64106, USA

Received 10 September 2012; Accepted 26 September 2012

Academic Editors: K. Higa and C.-T. Wu

Copyright © 2012 Andrew J. Montalbano et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

receptor activity is directly modulated by glyceraldehyde 3-phosphate dehydrogenase (GAPDH), a protein with many nonglycolytic moonlighting functions. In addition to playing a role in the phosphorylation of the receptor, GAPDH may also participate in proper receptor trafficking to the plasma membrane. We previously showed that volatile anesthetics affect GAPDH structure and function that may contribute to the manner by which GAPDH modulates the receptor. In the current study, GAPDH interacted with engineered phospholipid-containing vesicles, preferring association with phosphatidylserine over phosphatidylcholine. Phosphatidyl-serine is known to participate in membrane trafficking of transport proteins and to play a role in receptor stability and function. We observed that GAPDH promoted the self-association and fusion of phosphatidyl-serine-rich vesicles as well as decreased membrane fluidity. Isoflurane enhanced each of these GAPDH-mediated events. Isoflurane also increased the binding of GAPDH to the cytoplasmic loop of the receptor. These observations are consistent with the working model of isoflurane playing a role in the trafficking of membrane proteins. This study is the first to implicate GAPDH and isoflurane in the regulation of receptor localization, providing insight into the mechanism of action of anesthesia.