Theses and Dissertations

Date of Award

5-2022

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biochemistry and Molecular Biology

First Advisor

Dr. Xiaoqian Fang

Second Advisor

Dr. Andrew Tsin

Third Advisor

Dr. Yonghong Zhang

Abstract

Postsynaptic density-95 (PSD-95) is a membrane-associated guanylate kinase that mediates localization of receptors in the excitatory postsynaptic density. It has been reported that PSD-95 mediates postsynaptic localization of NMDA receptors and anchors postsynaptic AMPAR receptors mainly through its postsynaptic membrane targeting by its N-terminal palmitoylation. Recent studies have shown that Ca2+/calmodulin blocks palmitoylation of PSD-95 by binding at the N-terminus of PSD-95, which promotes dissociation of PSD-95 from the postsynaptic membrane and causes loss of surface AMPARs in cultured neurons. Another metal ion zinc is found in various areas of the brain. As an endogenous neuromodulator, zinc plays a role in synaptic transmission and is important in the maintenance of postsynaptic density stability. However, whether or not Zn2+ interacts with PSD-95 and regulates PSD-95 modification remain unknown. This study was carried out in human embryonic kidney 293 (HEK-293) cells. Cells were transfected with PSD-95 plasmids. After incubation for 48 hours, the cells were stimulated with 0.1 mM ZnCl2 for 5 min. And then the cells were harvested and the palmitoylation of PSD-95 was assessed using acyl-biotinyl exchange (ABE) method and Western blot. Our data showed that zinc stimulation decreased PSD-95 palmitoylation by 40%. The potential effect of the Zn2+-induced depalmitoylation of PSD-95 will be further studied, such as PSD-95 postsynaptic stability and PSD-95 postsynaptic localization. And more work needs to be done to unveil the mechanism underlying the impact of the depalmitoylation of PSD-95 on the postsynaptic localization of NMDARs and AMPRs in response to zinc stimulation.

Comments

Copyright 2022 Luis F. Acosta. All Rights Reserved.

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