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First published online 15 April 2003
doi: 10.1242/jcs.00429
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Research Article |
Department of Physiology, University of Arizona, Tucson, AZ 85724, USA
* Author for correspondence (e-mail: amsimon{at}u.arizona.edu)
Accepted 13 February 2003
Vascular endothelial cells are coupled by gap junctions that permit
cell-to-cell transfer of small molecules, including signals that may be
important for vasomotor responses. Connexin37 (Cx37) and connexin40 (Cx40) are
the predominant gap-junction proteins present in mouse endothelium. We
examined the effect of eliminating Cx37, Cx40, or both, on interendothelial
communication in mouse aorta. Intercellular transfer of biocytin and
[2-(4-nitro-2,1,3-benzoxadiazol-7-yl)aminoethyl]trimethylammonium (NBD-TMA)
was used to assess gap-junction-mediated coupling. Ablation of Cx40 generally
had a greater effect on dye-transfer than ablation of Cx37. The effect of Cx40
ablation on dye-transfer was age dependent. There was a 27-fold reduction in
biocytin transfer in embryonic Cx40–/– aortic
endothelium, a much larger change than in aortas of 6-7-week-old
Cx40–/– animals, which showed a 3.5-fold reduction. By
contrast, there was no reduction in biocytin transfer in embryonic
Cx37–/– endothelium. Embryonic aortas lacking both Cx37
and Cx40 showed a complete loss of endothelial dye-transfer. Surprisingly,
elimination of Cx40 resulted in up to a 17-fold drop in endothelial Cx37 on
western blots, whereas deletion of Cx37 reduced endothelial Cx40 up to
4.2-fold. By contrast, in the medial layer, both Cx37 and Cx43 increased
fourfold in Cx40–/– aortas. Declines in
non-ablated endothelial connexins were not mediated by changes in connexin
mRNA levels, suggesting a post-transcriptional effect. Our results indicate
that Cx37 and Cx40 are the only functional connexins expressed in mouse aortic
endothelium and are collectively crucial for endothelial communication.
Furthermore, Cx37 and Cx40 are codependent on each other for optimal
expression in vascular endothelium.
Key words: Connexin37, Connexin40, Gap junction, Intercellular communication, Aorta, Endothelium
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