Date of Award
Spring 6-12-2026
Document Type
Dissertation
Degree Name
Ph.D. in Biological Sciences
Organizational Unit
College of Natural Science and Mathematics, Biological Sciences
First Advisor
Yan Qin
Second Advisor
Scott Barbee
Third Advisor
Daniel Linseman
Fourth Advisor
Martin Margittai
Copyright Statement / License for Reuse
All Rights Reserved.
Keywords
Zinc, Endogenous zinc mobilization, Microtubule stability, Signaling molecule
Abstract
Zinc (Zn²⁺) is an essential trace metal. It plays critical roles in cellular structure, enzymatic activity, and intracellular signaling. Traditionally, zinc is seen as a structural cofactor. However, emerging evidence suggests it may also act as a dynamic signaling molecule. The mechanisms controlling endogenous zinc mobilization and its effects in living cells remain largely undefined. In this dissertation, I investigate these mechanisms and roles using genetically encoded and small-molecule fluorescent sensors. First, I demonstrate that metallothionein III (MT3) mediates Ca²⁺-dependent Zn²⁺ release in neurons. This mechanism shows how calcium signaling can transiently increase cytosolic zinc. These Zn²⁺ spikes inhibit dendritic arborization, revealing a functional link between zinc signaling and neuronal development. Next, I show that isothiocyanates mobilize intracellular pools of buffered zinc in living cells. This identifies a new way to study pools of loosely bound zinc. It also highlights the disruption of zinc-buffering systems in pathological conditions. Finally, I explore the interaction between zinc and the microtubule cytoskeleton. My results show that elevated cytosolic Zn²⁺ perturbs microtubule dynamics. This increases microtubule stability and can protect them from depolymerization. This offers a new pathway for how zinc dysregulation can impair cellular processes. It also provides a new opportunity to use zinc to enhance current therapeutics. Together, this work shows that zinc is not only a structural ion but also a tightly regulated signaling molecule and a regulator of the cytoskeleton. These findings expand our understanding of endogenous zinc signaling pathways and reveal new mechanisms by which zinc affects neuronal development and cellular function.
Copyright Date
6-2026
Publication Statement
Copyright is held by the author. User is responsible for all copyright compliance.
Rights Holder
Lyndsie Salvagio
Provenance
Received from ProQuest
File Format
application/pdf
Language
English (eng)
Extent
175 pgs
File Size
4.6 MB
Recommended Citation
Salvagio, Lyndsie, "Uncovering Endogenous Zinc Dynamics and Signaling in Living Cells" (2026). Electronic Theses and Dissertations. 2744.
https://digitalcommons.du.edu/etd/2744