Abstract
GABAA 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 GABAA 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 GABAA 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 GABAA 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 GABAA receptor localization, providing insight into the mechanism of action of anesthesia.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.