Please use this identifier to cite or link to this item:
https://scholarbank.nus.edu.sg/handle/10635/209757
DC Field | Value | |
---|---|---|
dc.title | POST-TRANSCRIPTIONAL MODIFICATIONS OF CAV1.3 CHANNEL DIVERSIFY ITS ROLE IN PRESYNAPTIIC MECHANISMS | |
dc.contributor.author | WONG RUIXIONG | |
dc.date.accessioned | 2021-12-07T18:00:22Z | |
dc.date.available | 2021-12-07T18:00:22Z | |
dc.date.issued | 2021-08-04 | |
dc.identifier.citation | WONG RUIXIONG (2021-08-04). POST-TRANSCRIPTIONAL MODIFICATIONS OF CAV1.3 CHANNEL DIVERSIFY ITS ROLE IN PRESYNAPTIIC MECHANISMS. ScholarBank@NUS Repository. | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/209757 | |
dc.description.abstract | CaV1.3 (CACNA1D) is a voltage-gated calcium channel (VGCC) with diverse roles and functions, ranging from the generalized conductance of Ca2+ transients in neuronal cells to more specialized tasks such as endocrine secretion in adrenal chromaffin cells and auditory transduction in hair cells. While studies have remained largely focused on elucidating these primary roles of CaV1.3 in either physiological or pathological settings, the fine tuning of CaV1.3 function contributed by post-transcriptional modifications (such as splice variation and RNA editing) is much less well appreciated. In this dissertation, we present three studies in line with this narrative, one at the pre-synaptic and two at the post-synaptic termini. At the pre-synaptic terminus, we show how splice variation in the I-II loop and C-terminus of CaV1.3 augments its interaction with a pre-synaptic protein, snapin, leading to increased current density that is further mitigated by a corresponding increase in CaV1.3 surface expression and decrease in proteasomal degradation. At the post-synaptic terminus, we first focused on learning and memory phenotypes associated with mice lacking in RNA editing complementary sequence (ECS) of CaV1.3 (CaV1.3ECS). CaV1.3ECS mice showed decreased latency in locating the submerged platform in the Morris Water Maze, which corresponded with an observed increase in synaptic strength during the sustained phase of late-LTP (L-LTP) in extracellular field recordings. Interestingly, while these mice show characteristic increases in pCaMKIIα/CaMKIIα and pCREB/CREB ratios post-learning, they also show increased proBDNF expression in hippocampal CA1. We thereafter conducted a second study which focused on fear phenotypes associated with CaV1.3ECS mice, which initially exhibit normal acquisition of contextual fear memory, but subsequently show diminished latency in spontaneous extinction of that same fear memory. Taken together, these findings demonstrate the complexity in strategies adopted by cellular processes to fine tune CaV1.3 properties, highlighting the importance of splice variation in mediating protein-protein interactions and challenging the current understanding of CaV1.3 and RNA editing involvement in learning and memory processes. | |
dc.language.iso | en | |
dc.subject | CALCIUM CHANNEL, CAV1.3, ALTERNATIVE SPLICING, SNAPIN, RNA EDITING, LEARNING AND MEMORY, ANXIETY, FEAR | |
dc.type | Thesis | |
dc.contributor.department | INTEGRATIVE SCIENCES & ENGINEERING PROG | |
dc.contributor.supervisor | Tuck Wah Soong | |
dc.description.degree | Ph.D | |
dc.description.degreeconferred | DOCTOR OF PHILOSOPHY (NUSGS) | |
Appears in Collections: | Ph.D Theses (Open) |
Show simple item record
Files in This Item:
File | Description | Size | Format | Access Settings | Version | |
---|---|---|---|---|---|---|
WongRX.pdf | 6.39 MB | Adobe PDF | OPEN | None | View/Download |
Google ScholarTM
Check
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.