3 results
Loss of melanoregulin (MREG) enhances cathepsin-D secretion by the retinal pigment epithelium
- LAURA S. FROST, VANDA S. LOPES, FRANK P. STEFANO, ALVINA BRAGIN, DAVID S. WILLIAMS, CLAIRE H. MITCHELL, KATHLEEN BOESZE-BATTAGLIA
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- Journal:
- Visual Neuroscience / Volume 30 / Issue 3 / May 2013
- Published online by Cambridge University Press:
- 23 April 2013, pp. 55-64
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- Article
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Cathepsin-D (Cat-D) is a major proteolytic enzyme in phagocytic cells. In the retinal pigment epithelium (RPE), it is responsible for the daily degradation of photoreceptor outer segments (POSs) to maintain retinal homeostasis. Melanoregulin (MREG)-mediated loss of phagocytic capacity has been linked to diminished intracellular Cat-D activity. Here, we demonstrate that loss of MREG enhances the secretion of intermediate Cat-D (48 kDa), resulting in a net enhancement of extracellular Cat-D activity. These results suggest that MREG is required to maintain Cat-D homeostasis in the RPE and likely plays a protective role in retinal health. In this regard, in the Mregdsu/dsu mouse, we observe increased basal laminin. Loss of the Mregdsu allele is not lethal and therefore leads to slow age-dependent changes in the RPE. Thus, we propose that this model will allow us to study potential dysregulatory functions of Cat-D in retinal disease.
Contributors
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- By Douglas L. Arnold, Laura J. Balcer, Amit Bar-Or, Sergio E. Baranzini, Frederik Barkhof, Robert A. Bermel, Francois A. Bethoux, Dennis N. Bourdette, Richard K. Burt, Peter A. Calabresi, Zografos Caramanos, Tanuja Chitnis, Stacey S. Cofield, Jeffrey A. Cohen, Nadine Cohen, Alasdair J. Coles, Devon Conway, Stuart D. Cook, Gary R. Cutter, Peter J. Darlington, Ann Dodds-Frerichs, Ranjan Dutta, Gilles Edan, Michelle Fabian, Franz Fazekas, Massimo Filippi, Elizabeth Fisher, Paulo Fontoura, Corey C. Ford, Robert J. Fox, Natasha Frost, Alex Z. Fu, Siegrid Fuchs, Kazuo Fujihara, Kristin M. Galetta, Jeroen J.G. Geurts, Gavin Giovannoni, Nada Gligorov, Ralf Gold, Andrew D. Goodman, Myla D. Goldman, Jenny Guerre, Stephen L. Hauser, Peter B. Imrey, Douglas R. Jeffery, Stephen E. Jones, Adam I. Kaplin, Michael W. Kattan, B. Mark Keegan, Kyle C. Kern, Zhaleh Khaleeli, Samia J. Khoury, Joep Killestein, Soo Hyun Kim, R. Philip Kinkel, Stephen C. Krieger, Lauren B. Krupp, Emmanuelle Le Page, David Leppert, Scott Litwiller, Fred D. Lublin, Henry F. McFarland, Joseph C. McGowan, Don Mahad, Jahangir Maleki, Ruth Ann Marrie, Paul M. Matthews, Francesca Milanetti, Aaron E. Miller, Deborah M. Miller, Xavier Montalban, Charity J. Morgan, Ichiro Nakashima, Sridar Narayanan, Avindra Nath, Paul W. O’Connor, Jorge R. Oksenberg, A. John Petkau, Michael D. Phillips, J. Theodore Phillips, Tammy Phinney, Sean J. Pittock, Sarah M. Planchon, Chris H. Polman, Alexander Rae-Grant, Stephen M. Rao, Stephen C. Reingold, Maria A. Rocca, Richard A. Rudick, Amber R. Salter, Paula Sandler, Jaume Sastre-Garriga, John R. Scagnelli, Dana J. Serafin, Lynne Shinto, Nancy L. Sicotte, Jack H. Simon, Per Soelberg Sørensen, Ryan E. Stagg, James M. Stankiewicz, Lael A. Stone, Amy Sullivan, Matthew Sutliff, Jessica Szpak, Alan J. Thompson, Bruce D. Trapp, Helen Tremlett, Maria Trojano, Orla Tuohy, Rhonda R. Voskuhl, Marc K. Walton, Mike P. Wattjes, Emmanuelle Waubant, Martin S. Weber, Howard L Weiner, Brian G. Weinshenker, Bianca Weinstock-Guttman, Jeffrey L. Winters, Jerry S. Wolinsky, Vijayshree Yadav, E. Ann Yeh, Scott S. Zamvil
- Edited by Jeffrey A. Cohen, Richard A. Rudick
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- Book:
- Multiple Sclerosis Therapeutics
- Published online:
- 05 December 2011
- Print publication:
- 20 October 2011, pp viii-xii
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5 - The F-plasmid, a paradigm for bacterial conjugation
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- By Michael J. Gubbins, Department of Biological Sciences, University of Alberta, William R. Will, Department of Biological Sciences, University of Alberta, Laura S. Frost, Department of Biological Sciences, University of Alberta
- Edited by Peter Mullany, University College London
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- Book:
- The Dynamic Bacterial Genome
- Published online:
- 06 August 2009
- Print publication:
- 26 September 2005, pp 151-206
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Summary
The F factor is often associated with Escherichia coli and appears to have been adapted by the bacterial host to act as an agent of genetic exchange and evolution. F encodes a type IV secretion system (T4SS) that enables bacterial conjugation, the transfer of DNA from a donor F+ to a recipient F− cell. The delivery of DNA containing either host or foreign genes has important consequences for the bacterium, allowing it to enlarge or modify its genetic content and rapidly adapt to an environmental niche. Unlike other plasmids, the conjugative functions of F and F-like plasmids appear to be controlled by a complex regulatory network that involves many host proteins resulting in a symbiotic relation between F and its host. This chapter outlines the predicted and known functions for all the genes on the F plasmid and its close relatives, and describes our current knowledge about the regulation of F conjugation.
BRIEF HISTORY OF THE F PLASMID
The discovery of horizontal gene transfer between bacteria can be attributed to the work of Lederberg and Tatum (1946), who observed that different strains of E. coli K-12 could be genetically and phenotypically altered when mixed together. A series of experiments led to the conclusion that direct contact between bacteria was required in order for genetic material to be transferred between the cells (Davis, 1950). This transfer was found to occur in one direction, from donor to recipient cells, by a mechanism contained within the donor cells (Hayes, 1952).