HIV-1 Tat Affects Interorganelle Communication in HIV-Associated Neurocognitive Disorders (HAND)
| Autor: | Arjona, Sterling P. |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: | |
| Druh dokumentu: | Text |
| DOI: | 10.34944/dspace/8034 |
| Popis: | 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 Ph.D. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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