REGULATORY MECHANISMS OF SLC39A4 (ZIP4) AND SLC39A5 (ZIP5) IN THE ADAPTIVE RESPONSE TO ZINC AVAILABILITY
Issue Date
2009-04-06Author
Weaver, Benjamin Patrick
Publisher
University of Kansas
Format
283 pages
Type
Dissertation
Degree Level
Ph.D.
Discipline
Biochemistry & Molecular Biology
Rights
This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
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Show full item recordAbstract
The aims of this research were to determine how Zip4 and Zip5 are regulated in response to zinc availability and how Zip4 impacts development. Loss of Zip4 resulted in embryonic lethality. Heterozygosity negatively affected eye, heart, and brain development. Excess zinc did not rescue lethality but ameliorated the heterozygous effects. Zip4 and Zip5 had reciprocal regulation in response to zinc availability. Zip4 expression was regulated by stability of the mRNA and protein: both accumulate during zinc deficiency; ZIP4 was rapidly internalized then degraded following zinc repletion. The Zip5 mRNA levels did not change with zinc availability and were polysome-associated. ZIP5 accumulated on the basolateral membranes after zinc repletion. miRNAs predicted to target Zip5 in an accessible region of the conserved 3' UTR were polysome-associated in all tissues that regulate Zip5. Zip4 and Zip5 are both regulated by post-transcriptional mechanisms in response to zinc availability and Zip4 is essential for development.
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