QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 15, Issue 11, 4761-4774, November 2004

This Article Full Text Full Text (PDF) All Versions of this Article: E04-03-0271v1 15/11/4761    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ozog, M. A. Articles by Naus, C. C.G. Search for Related Content PubMed PubMed Citation Articles by Ozog, M. A. Articles by Naus, C. C.G.

The Complex of Ciliary Neurotrophic Factor-Ciliary Neurotrophic Factor Receptor Up-Regulates Connexin43 and Intercellular Coupling in Astrocytes via the Janus Tyrosine Kinase/Signal Transducer and Activator of Transcription Pathway

Mark A. Ozog ^*, Suzanne M. Bernier , Dave C. Bates , Bishwanath Chatterjee , Cecilia W. Lo , and Christian C.G. Naus ^* 

^* Department of Anatomy and Cell Biology, The University of British Columbia, Vancouver, British Columbia, Canada; Canadian Institutes of Health Research Group in Skeletal Development and Remodeling, Department of Anatomy and Cell Biology, The University of Western Ontario, London, Ontario V6T 1Z3, Canada; and Laboratory of Developmental Biology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892-8019

Submitted May 2, 2003; Revised June 4, 2004; Accepted June 22, 2004
Monitoring Editor: Keith Mostov

Cytokines regulate numerous cell processes, including connexin expression and gap junctional coupling. In this study, we examined the effect of ciliary neurotrophic factor (CNTF) on connexin43 (Cx43) expression and intercellular coupling in astrocytes. Murine cortical astrocytes matured in vitro were treated with CNTF (20 ng/ml), soluble ciliary neurotrophic factor receptor (CNTFR) (200 ng/ml), or CNTF-CNTFR. Although CNTF and CNTFR alone had no effect on Cx43 expression, the heterodimer CNTF-CNTFR significantly increased both Cx43 mRNA and protein levels. Cx43 immunostaining correlated with increased intercellular coupling as determined by dye transfer analysis. By using the pharmacological inhibitor -cyano-(3,4-dihydroxy)-N-benzylcinnamide (AG490), the increase in Cx43 was found to be dependent on the Janus tyrosine kinase/signal transducer and activator of transcription (JAK/STAT) pathway. Immunocytochemical analysis revealed that CNTF-CNTFR treatment produced nuclear localization of phosphorylated STAT3, whereas CNTF treatment alone did not. Transient transfection of constructs containing various sequences of the Cx43 promoter tagged to a LacZ reporter into ROS 17/2.8 cells confirmed that the promoter region between -838 to -1693 was deemed necessary for CNTF-CNTFR to induce heightened expression. CNTF-CNTFR did not alter Cx30 mRNA levels, suggesting selectivity of CNTF-CNTFR for connexin signaling. Together in the presence of soluble receptor, CNTF activates the JAK/STAT pathway leading to enhanced Cx43 expression and intercellular coupling.

The online version of this article contains supplementary material accessible through http://www.molbiolcell.org.

Corresponding author. E-mail address: cnaus{at}interchange.ubc.ca.

This article has been cited by other articles:

				M. A. Ozog, G. Modha, J. Church, R. Reilly, and C. C. Naus Co-administration of Ciliary Neurotrophic Factor with Its Soluble Receptor Protects against Neuronal Death and Enhances Neurite Outgrowth J. Biol. Chem., March 7, 2008; 283(10): 6546 - 6560. [Abstract] [Full Text] [PDF]

				C. P.K. Lai, J. F. Bechberger, R. J. Thompson, B. A. MacVicar, R. Bruzzone, and C. C. Naus Tumor-Suppressive Effects of Pannexin 1 in C6 Glioma Cells Cancer Res., February 15, 2007; 67(4): 1545 - 1554. [Abstract] [Full Text] [PDF]