Mechanisms of asymetric localization of VDUP1 in neuronal stem cells and progeny
Issue Date
2020-07
Authors
Hamersky, Michael IV '20
Degree
MS in Pharmaceutical Sciences
Advisor
Dearborn, Richard E.
Committee Members
Voigt, Jeffrey M.
LaRocca, Timothy
LaRocca, Timothy
Journal Title
Journal ISSN
Volume Title
Abstract
Vitamin D3 Upregulated Protein 1 (VDUP1; also known as thioredoxin interacting protein TXNIP) is a tumor suppressor protein whose expression is downregulated in certain types of cancer. VDUP1 will actively bind to thioredoxin (TRX) reducing its ability to inhibit reactive oxygen species (ROS). When VDUP1 activity is suppressed, TRX binds to ROS, disabling one the cell\342\200\231s natural apoptotic pathway. VDUP1 expression also regulates several physiological functions as well as play a key role in asymmetric cell division. Drosophila Melanogaster is the model used due to its fast reproduction and VDUP1 homolog to that of humans. VDUP1\342\200\231s impact on neuroblast (NB) proliferation and central nervous system (CNS) development has previously been studied, while the mechanism remains unexplored. Miranda (Mira), a cargo adaptor protein used for cellular differentiation, is a protein known to move from the NB to progeny ganglionic mother cell (GMC) during asymmetric division. VDUP1 shares the same localization pattern, a crescent shape along the basal membrane of the NB, that Mira has. Downregulation of VDUP1 also results in a decrease in Prospero (Pros), a cell fate determinate protein, which attaches itself to Mira during asymmetric division. Using mutated Mira Drosophila lines, VDUP1 distribution was altered and viewed via immunocytochemistry (ICC) and confocal imaging. When Mira lacked the ability to bind cargo/localize to the basal membrane, VDUP1 was unable to properly be distributed to the daughter NB and progeny GMC. A UAS-GAL4 system in combination with VDUP1 allowed for imaging of VDUP1 during gain of function (GOF). Interestingly, green fluorescent protein positive (GFP+) cells were rare and showed textbook characteristics of apoptosis. The collected data, along with previous studies, shows high correlation between VDUP1 and Mira colocalization through direct interaction. It also confirmed VDUP1\342\200\231s ability to induce apoptosis in cells at a high rate.
Citation
Hamersky M. Mechanisms of asymetric localization of VDUP1 in neuronal stem cells and progeny [thesis]. Ann Arbor (MI): Proquest LLC; 2020. 55 p.
ACPHS Research Commons URI
Description
Click on the Resource Link to find this item in the ACPHS Library catalog.