Document Type
Dissertation
Date of Award
2021
Degree Name
Doctor of Philosophy (PhD)
Department
Basic Biomedical Science
First Advisor
Randolph Faustino
Abstract
The nuclear pore complex (NPC) is a highly conserved, yet dynamic structure within the cell. As the sole point of communication between the nucleus and cytoplasm, maintenance of its function and composition is essential. Recent studies have shown that both NPCs and their constitutive components, nucleoporins (NUPs), can have diverse roles separate from canonical transport. In addition, mutations in individual NUPs have been linked to a wide variety of clinical diseases, however, the exact mechanism by which they cause pathology is often unclear. Recently, a point mutation in NUP155, R391H, was identified specifically in patients with familial atrial fibrillation. We hypothesize that the R391H mutation in NUP155 alters a key aspect of its cellular function, impacting NPC transport, localization dynamics and/or protein-protein interactions associated with disease pathogenesis. To clear up previously reported contradictions, we used fluorescence-based techniques to evaluate the canonical function, localization, and mobility of NUP155 and the R391H mutant in vitro. We demonstrate that the expression of the R391H mutant does not alter canonical nucleocytoplasmic transport or significantly impair the localization and mobility of NUP155 at the nuclear envelope. Further, we employed BioID to establish the NUP155 interactome and identify perturbations that result from the R391H mutation. Our results suggest that in addition to the expected NPC associated proteins, NUP155 interacts with, or is in close proximity to, a variety of proteins associated with mitochondrial function and cellular metabolism. Interestingly, a sub-set of these interactions are lost in the R391H mutant. The results presented in this dissertation identify NUP155 as a stable component of the nuclear pore and identify protein-protein interactions that point to a potential new role for NUP155 in influencing cellular energetics.
Subject Categories
Biology
Keywords
The nuclear pore complex (NPC) is a highly conserved, yet dynamic structure within the cell
Number of Pages
178
Publisher
University of South Dakota
Recommended Citation
Storm, Emily, "Characterizing the Cellular Dynamics of NUP155 and a Clinically Identified Variant" (2021). Dissertations and Theses. 319.
https://red.library.usd.edu/diss-thesis/319
