Molecular Biology of the Cell Sign up for new MBC in Press e-TOCs!

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
 QUICK SEARCH:   [advanced]


     


This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Song, Y.
Right arrow Articles by Silverman, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Song, Y.
Right arrow Articles by Silverman, M.

Vol. 10, Issue 5, 1609-1619, May 1999

Human munc13 Is a Diacylglycerol Receptor that Induces Apoptosis and May Contribute to Renal Cell Injury in Hyperglycemia

Yong Song, Menachem Ailenberg, and Mel Silverman*

Medical Research Council Membrane Biology Group, Department of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada

We have previously shown that human munc13 (hmunc13) is up-regulated by hyperglycemia under in vitro conditions in human mesangial cell cultures. The purpose of the present study was to determine the cellular function of hmunc13. To do this, we have investigated the subcellular localization of hmunc13 in a transiently transfected renal cell line, opossum kidney cells. We have found that hmunc13 is a cytoplasmic protein and is translocated to the Golgi apparatus after phorbol ester stimulation. In addition, cells transfected with hmunc13 demonstrate apoptosis after treatment with phorbol ester, but cells transfected with an hmunc13 deletion mutant in which the diacylglycerol (C1) binding domain is absent exhibit no change in intracellular distribution and no induction of apoptosis in the presence of phorbol ester stimulation. We conclude that both the diacylglycerol-induced translocation and the apoptosis represent functional activity of hmunc13. We have also demonstrated that munc13-1 and munc13-2 are localized mainly to cortical epithelial cells in rat kidney and both are overexpressed under conditions of hyperglycemia in a streptozotocin-treated diabetic rat model. Taken together, our data suggest that hmunc13 serves as a diacylglycerol-activated, PKC-independent signaling pathway capable of inducing apoptosis and that this pathway may contribute to the renal cell complications of hyperglycemia.


*   Corresponding author. E-mail address: melvin.silverman{at}utoronto.ca.


Molecular Biology of the Cell
Vol. 10, 1609-1619, May 1999
Copyright © 1999 by The American Society for Cell Biology



This article has been cited by other articles:


Home page
Mol. Biol. CellHome page
N. M. Goldenberg, S. Grinstein, and M. Silverman
Golgi-bound Rab34 Is a Novel Member of the Secretory Pathway
Mol. Biol. Cell, December 1, 2007; 18(12): 4762 - 4771.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
K. P. Becker and Y. A. Hannun
cPKC-dependent Sequestration of Membrane-recycling Components in a Subset of Recycling Endosomes
J. Biol. Chem., December 26, 2003; 278(52): 52747 - 52754.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
Q. Zhang, H. K. Chieu, C. P. Low, S. Zhang, C. K. Heng, and H. Yang
Schizosaccharomyces pombe Cells Deficient in Triacylglycerols Synthesis Undergo Apoptosis upon Entry into the Stationary Phase
J. Biol. Chem., November 21, 2003; 278(47): 47145 - 47155.
[Abstract] [Full Text] [PDF]


Home page
Mol. Pharmacol.Home page
M. G. Kazanietz
Novel "Nonkinase" Phorbol Ester Receptors: The C1 Domain Connection
Mol. Pharmacol., April 1, 2002; 61(4): 759 - 767.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
H. Wang and M. G. Kazanietz
Chimaerins, Novel Non-protein Kinase C Phorbol Ester Receptors, Associate with Tmp21-I (p23). EVIDENCE FOR A NOVEL ANCHORING MECHANISM INVOLVING THE CHIMAERIN C1 DOMAIN
J. Biol. Chem., February 1, 2002; 277(6): 4541 - 4550.
[Abstract] [Full Text] [PDF]


Home page
Mol. Biol. CellHome page
R. E. Kohn, J. S. Duerr, J. R. McManus, A. Duke, T. L. Rakow, H. Maruyama, G. Moulder, I. N. Maruyama, R. J. Barstead, and J. B. Rand
Expression of Multiple UNC-13 Proteins in the Caenorhabditis elegans Nervous System
Mol. Biol. Cell, October 1, 2000; 11(10): 3441 - 3452.
[Abstract] [Full Text]


Home page
J. Biol. Chem.Home page
M. J. Caloca, H. Wang, A. Delemos, S. Wang, and M. G. Kazanietz
Phorbol Esters and Related Analogs Regulate the Subcellular Localization of beta 2-Chimaerin, a Non-protein Kinase C Phorbol Ester Receptor
J. Biol. Chem., May 18, 2001; 276(21): 18303 - 18312.
[Abstract] [Full Text] [PDF]




Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]