spacer gif spacer gif spacer gif spacer gif spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search    

The fully linked HTML version of this article has now been published.
JCS ePress online publication date 17 Jan 2006
doi: 10.1242/jcs.02770

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jcs.02770v1
119/3/532    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
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 Lai, A.
Right arrow Articles by Charles, A. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lai, A.
Right arrow Articles by Charles, A. C.

Research Article

Oculodentodigital dysplasia connexin43 mutations result in non-functional connexin hemichannels and gap junctions in C6 glioma cells


Albert Lai*, Dung-Nghi Le, William A. Paznekas, Wes D. Gifford, Ethylin Wang Jabs, and Andrew C. Charles
* Author for correspondence (e-mail: albertlai{at}mednet.ucla.edu)

Oculodentodigital dysplasia (ODDD) is a rare developmental disorder characterized by craniofacial and limb abnormalities. Over 35 separate mutations in human connexin43 (Cx43) causing ODDD have been identified. Several mutations are also associated with central nervous system involvement, including white-matter changes detected by magnetic resonance imaging. As Cx43 is abundantly expressed in astrocytes, we hypothesized that the mutant Cx43 proteins that produce neurological dysfunction have abnormal functional characteristics in astrocytes. To understand how ODDD-associated mutations affect Cx43 signaling in cells of glial origin, we conducted studies in rat C6 glioma cells, a communication-deficient glial cell line that expresses low levels of Cx43. We generated stable cell lines expressing enhanced yellow fluorescent protein (eYFP)-tagged human Cx43 constructs encoding wild-type and six eYFP-tagged mutant Cx43 mutants: Y17S, G21R, A40V, F52dup, L90V and I130T. Of these, Y17S, L90V and I130T are associated with neurological abnormalities. We found that all mutants could be detected on the cell surface. Y17S, G21R, A40V, L90V and I130T formed triton-resistant plaques representing gap junctions, although the relative ability to form plaques was decreased in these mutants compared with the wild type. F52dup formed dramatically reduced numbers of plaques. Propidium iodide uptake experiments demonstrated that all mutants were associated with reduced connexin hemichannel function compared with wild type. Scrape-loading experiments performed on the same stable cell lines showed reduced gap junctional dye transfer in all mutants compared with the wild type. These studies demonstrated that ODDD-associated Cx43 mutations result in non-functional connexin hemichannels and gap junction functions in a glial cell line regardless of whether the particular mutant is associated with neurological dysfunction.


This article has been cited by other articles:


Home page
 Hum Mol GenetHome page
R. Dobrowolski, P. Sasse, J. W. Schrickel, M. Watkins, J.-S. Kim, M. Rackauskas, C. Troatz, A. Ghanem, K. Tiemann, J. Degen, et al.
The conditional connexin43G138R mouse mutant represents a new model of hereditary oculodentodigital dysplasia in humans
Hum. Mol. Genet., February 14, 2008; 17(4): 539 - 554.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
D. W. Laird
Closing the Gap on Autosomal Dominant Connexin-26 and Connexin-43 Mutants Linked to Human Disease
J. Biol. Chem., February 8, 2008; 283(6): 2997 - 3001.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
N. Kalcheva, J. Qu, N. Sandeep, L. Garcia, J. Zhang, Z. Wang, P. D. Lampe, S. O. Suadicani, D. C. Spray, and G. I. Fishman
Gap junction remodeling and cardiac arrhythmogenesis in a murine model of oculodentodigital dysplasia
PNAS, December 18, 2007; 104(51): 20512 - 20516.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Y. Zhou, W. Yang, M. M. Lurtz, Y. Ye, Y. Huang, H.-W. Lee, Y. Chen, C. F. Louis, and J. J. Yang
Identification of the Calmodulin Binding Domain of Connexin 43
J. Biol. Chem., November 30, 2007; 282(48): 35005 - 35017.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
D. Tong, T. Y. Li, K. E. Naus, D. Bai, and G. M. Kidder
In vivo analysis of undocked connexin43 gap junction hemichannels in ovarian granulosa cells
J. Cell Sci., November 15, 2007; 120(22): 4016 - 4024.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
X.-Q. Gong, Q. Shao, S. Langlois, D. Bai, and D. W. Laird
Differential Potency of Dominant Negative Connexin43 Mutants in Oculodentodigital Dysplasia
J. Biol. Chem., June 29, 2007; 282(26): 19190 - 19202.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
D. J. Belliveau, M. Bani-Yaghoub, B. McGirr, C. C. G. Naus, and W. J. Rushlow
Enhanced Neurite Outgrowth in PC12 Cells Mediated by Connexin Hemichannels and ATP
J. Biol. Chem., July 28, 2006; 281(30): 20920 - 20931.
[Abstract] [Full Text] [PDF]


© The Company of Biologists Ltd 2006