TRPM7 (Transient Receptor Potential Melastatin-like 7) is an ion channel necessary for the proper development of many cell types. Insight into the precise role of the channel in different cells has been hampered by the lethality of knocking out the gene in model organisms such as the mouse. Here I examine a zebrafish that has a loss-of-function mutation in the gene encoding Trpm7. First, I show that trpm7 is important for the function of developing dopaminergic neurons in the zebrafish. Second, I examine the interaction between trpm7 and the related gene vmat2 in order to develop a cellular mechanism of trpm7 function in presynaptic dopaminergic neurons. Finally, I investigate the necessity of the kinase and ion channel domains of trpm7 in their ability to promote pigmentation in melanophores as a model cell type. Based on the results from these experiments and observations from other researchers, I form a new hypothesis for Trpm7 function in protein sorting. These studies provide a detailed and novel analysis of the function of an ion channel that is necessary for life.
TRPM7 function in zebrafish dopaminergic neurons
Abstract
Details
- Title: Subtitle
- TRPM7 function in zebrafish dopaminergic neurons
- Creators
- Amanda R. Decker - University of Iowa
- Contributors
- Robert A. Cornell (Advisor)Tina Tootle (Committee Member)Amy Lee (Committee Member)Andrew Frank (Committee Member)Toshihiro Kitamoto (Committee Member)
- Resource Type
- Dissertation
- Degree Awarded
- Doctor of Philosophy (PhD), University of Iowa
- Degree in
- Anatomy and Cell Biology
- Date degree season
- Autumn 2015
- DOI
- 10.17077/etd.7i42ocad
- Publisher
- University of Iowa
- Number of pages
- x, 108 pages
- Copyright
- Copyright © 2015 Amanda R. Decker
- Language
- English
- Description illustrations
- illustrations (some color)
- Description bibliographic
- Includes bibliographical references (pages 95-108).
- Public Abstract (ETD)
Ion channels are molecules that maintain the correct balance of ions in living cells. TRP (Transient Receptor Potential) channels are one class of ion channels that includes TRPM7 (Transient Receptor Potential Melastatin-like7). The presence of TRPM7 is necessary to successfully pass important milestones during the early development of the embryo. Our work shows that trpm7 is also essential for the correct differentiation of two types of cells in the zebrafish: neurons that produce the neurotransmitter dopamine and the cells that produce pigment. My studies have focused on determining why Trpm7 is important in these cell types. I found that trpm7 mutant zebrafish exhibit many signs of impaired dopamine production. I propose that this ion channel is involved in creating intracellular compartments for the transport of potentially toxic substances such as dopamine and melanin. Because dopamine is an essential component of many healthy functions in the human brain, these studies may be of relevance to human health.
- Academic Unit
- Anatomy and Cell Biology
- Record Identifier
- 9983777125602771