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CONNEXINS AND PANNEXINS IN THE KIDNEY:
A STUDY OF THEIR EXPRESSION, REGULATION, AND FUNCTION
by
Fiona P Hanner
A Dissertation Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(SYSTEMS BIOLOGY AND DISEASE)
May 2010
Copyright 2010 Fiona P Hanner
Object Description
| Title | Connexins and pannexins in the kidney: a study of their expression, regulation, and function |
| Author | Hanner, Fiona P |
| Author email | fmccullo@usc.edu; fiona.hanner@gmail.com |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Systems Biology & Disease |
| School | Keck School of Medicine |
| Date defended/completed | 2010-03-15 |
| Date submitted | 2010 |
| Restricted until | Unrestricted |
| Date published | 2010-04-01 |
| Advisor (committee chair) | Peti-Peterdi, Janos |
| Advisor (committee member) |
Yu, Alan Kobielak, Agnieszka Sampath, Alapakkam Garner, Judy A. |
| Abstract | Connexins are the constituent proteins of a gap junction, a non-selective channel that links together two cells, allowing the passage of molecules directly between them. In addition, connexins are thought to form discrete “hemichannels” in uncoupled cells. This conformation permits molecular exchange between the intra- and extracellular environments. Pannexins are a structurally similar, but genetically unrelated class of proteins that appears to share the hemichannel-like structure and function of connexins, but does not engage in gap junction formation. Both connexins and pannexins are ubiquitously expressed and regulate intercellular communication, both through direct cell-cell coupling and via the release of secondary messengers such as ATP to the extracellular fluid. Gap junction coupling is well-established in the kidney and intercellular communication pathways that are critical to controlling major renal regulatory mechanisms are known to involve connexins and pannexins in other cell types. However, a systematic study of the expression and function of these proteins in the kidney has been absent. Therefore we sought to examine connexin and pannexin localization within the kidney and, based on these findings, investigate how they facilitate the signaling mechanisms and physiology at work in these regions. Based on initial reports of mRNA expression, we focused on four select isoforms. Chapters 1 and 2 delve into the expression and regulation of two connexins, Cx30 and Cx30.3, along the distal nephron. Finding expression of both isoforms in the apical membrane of the renal epithelial cells suggested a function for Cx30 and Cx30.3 as an ATP release mechanism which may regulate salt and water transport in the distal nephron through purinergic signaling. Chapter 3 details the expression of Cx45 in the juxtaglomerular apparatus.; After observing Cx45 localization in this region, we tested the hypothesis that Cx45 plays a role in regulating renin release and blood pressure by facilitating calcium wave propagation in the afferent arteriole vascular smooth muscle cells. Finally, Chapter 4 addresses the renal expression of the pannexin isoform Panx1 and presents data from renal epithelial cell cultures that demonstrate a role for Panx1 in the regulation of ATP release in the kidney. These studies have provided new insights into how connexins and pannexins are expressed in the kidney and suggest a significant role for these proteins in facilitating renal signaling mechanisms. Due to the importance of intercellular communication in the kidney, connexins and pannexins may ultimately have a profound downstream effect on key renal physiological phenomena. |
| Keyword | gap junction; hemichannel; intercellular communication; renal hemodynamics; calcium signaling; purinergic signaling; epithelial transport |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m2892 |
| Rights | Hanner, Fiona P |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | http://www.usc.edu/isd/libraries/services/ask_a_librarian/email/ |
| Filename | etd-Hanner-3601 |
| Archival file | uscthesesreloadpub_Volume23/etd-Hanner-3601.pdf |
Description
| Title | Page 1 |
| Full text | CONNEXINS AND PANNEXINS IN THE KIDNEY: A STUDY OF THEIR EXPRESSION, REGULATION, AND FUNCTION by Fiona P Hanner A Dissertation Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (SYSTEMS BIOLOGY AND DISEASE) May 2010 Copyright 2010 Fiona P Hanner |
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