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J. Biol. Chem., Vol. 281, Issue 44, 33163-33171, November 3, 2006

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 281/44/33163    most recent M606396200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend 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 Urschel, S. Articles by Willecke, K. Search for Related Content PubMed PubMed Citation Articles by Urschel, S. Articles by Willecke, K. Social Bookmarking                      What's this?

Protein Kinase A-mediated Phosphorylation of Connexin36 in Mouse Retina Results in Decreased Gap Junctional Communication between AII Amacrine Cells^*

Stephanie Urschel, Thorsten Höher, Timm Schubert, Cantas Alev^¶||**, Goran Söhl, Philipp Wörsdörfer, Takayuki Asahara^¶, Rolf Dermietzel^**, Reto Weiler, and Klaus Willecke¹

From the Institute of Genetics, University of Bonn, 53117 Bonn, Germany, the Institute of Biology, University of Oldenburg, Oldenburg, Germany, the ^¶Laboratory for Stem Cell Translational Research, RIKEN Center for Developmental Biology, 650-0047 Kobe, Japan, the ^||International Graduate School of Neuroscience (IGSN), 44780 Bochum, Germany, and the ^**Institute of Neuroanatomy and Molecular Brain Research, Ruhr-University Bochum, 44780 Bochum, Germany

Gap junctions in AII amacrine cells of mammalian retina participate in the coordination of the rod and cone signaling pathway involved in visual adaptation. Upon stimulation by light, released dopamine binds to D₁ receptors on AII amacrine cells leading to increased intracellular cAMP (cyclic adenosine monophosphate) levels. AII amacrine cells express the gap junctional protein connexin36 (Cx36). Phosphorylation of Cx36 has been hypothesized to regulate gap junctional activity of AII amacrine cells. However, until now in vivo phosphorylation of Cx36 has not been reported. Indeed, it had been concluded that Cx36 in bovine retina is not phosphorylated, but in vitro phosphorylation for Cx35, the bass ortholog of Cx36, had been shown. To clarify this experimental discrepancy, we examined protein kinase A (PKA)-induced phosphorylation of Cx36 in mouse retina as a possible mechanism to modulate the extent of gap junctional coupling. The cytoplasmic domains of Cx36 and the total Cx36 protein were phosphorylated in vitro by PKA. Mass spectroscopy revealed that all four possible PKA consensus motifs were phosphorylated; however, domains point mutated at the sites in question showed a prevalent usage of Ser-110 and Ser-293. Additionally, we demonstrated that Cx36 was phosphorylated in cultured mouse retina. Furthermore, activation of PKA increased the level of phosphorylation of Cx36. cAMP-stimulated, PKA-mediated phosphorylation of Cx36 protein was accompanied by a decrease of tracer coupling between AII amacrine cells. Our results link increased phosphorylation of Cx36 to down-regulation of permeability through gap junction channels mediating light adaptation in the retina.

Received for publication, July 5, 2006 , and in revised form, August 28, 2006.

^* Work in the Bonn laboratory was supported by a grant from the German Research Foundation (W:270/22-5,6) (to K. W.). Work in the Oldenburg laboratory was supported by a grant of the German Research Foundation (SFB 517, TP A2) (to R. W.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1–S5.

¹ To whom correspondence should be addressed: Institute of Genetics, University of Bonn, Römerstrasse 164, 53117 Bonn, Germany. Tel.: 49-228-734210; Fax: 49-228-734263; E-mail: genetik{at}uni-bonn.de.

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