Among Human Immunodeficiency viruses (HIV), type-1 (HIV-1) is the most common worldwide and has the highest virulence and infectivity. Though the virus only
infects a few cell types, the infection affects almost every organ system causing multiple
comorbidities. One of the comorbidities is HIV-associated Neurocognitive Disorders
(HAND). Interorganelle communication regulates many cellular functions including
calcium exchange, lipid exchange, intracellular trafficking, and mitochondrial
biogenesis. Interestingly, all these processes have been implicated in HAND suggesting
that dysregulation of interorganelle communication plays a role in the progression of
HAND. Using neuronal cell cultures, I show that mitochondrial-associated ER
membranes (MAM)-associated protein and MAM-tethering protein expression and
interactions are altered in the presence of the HIV-1 protein Tat. I also show, PTPIP51
and VAPB, two MAM-tethering proteins, expression is altered in the MAM fraction but
not the whole cell fraction, indicating a localization problem. Phosphorylation of
PTPIP51 has been shown to regulate the subcellular localization and I show that tyrosine
phosphorylation is upregulated with Tat. In addition, I show that PTPIP51 binding with
VAPB can be rescued with the addition of kinase inhibitors blocking PTPIP51
phosphorylation suggesting that Tat is altering the phosphorylation of PTPIP51 affecting
its subcellular localization and binding to VAPB. Furthermore, I show that ER-Golgi
communication is altered in the presence of Tat where there is an increase in the
interactions between YIF1A and VAPB, two ER-Golgi tethering proteins. The altered
iv
interactions between MAM and ER-Golgi tethering proteins in the presence of Tat lead
to the disruption of cellular pathways associated with dysfunctional interorganelle
communication that can lead to neuronal dysfunction and can contribute to HAND. / Biomedical Sciences
| Identifer | oai:union.ndltd.org:TEMPLE/oai:scholarshare.temple.edu:20.500.12613/8062 |
| Date | January 2022 |
| Creators | Arjona, Sterling P., 0000-0002-1543-5045 |
| Contributors | Sawaya, Bassel E., Selzer, Michael E., Ward, Sara Jane, Whelan, Kelly A. |
| Publisher | Temple University. Libraries |
| Source Sets | Temple University |
| Language | English |
| Detected Language | English |
| Type | Thesis/Dissertation, Text |
| Format | 129 pages |
| Rights | IN COPYRIGHT- This Rights Statement can be used for an Item that is in copyright. Using this statement implies that the organization making this Item available has determined that the Item is in copyright and either is the rights-holder, has obtained permission from the rights-holder(s) to make their Work(s) available, or makes the Item available under an exception or limitation to copyright (including Fair Use) that entitles it to make the Item available., http://rightsstatements.org/vocab/InC/1.0/ |
| Relation | http://dx.doi.org/10.34944/dspace/8034, Theses and Dissertations |
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