Title

Dopamine-stimulated dephosphorylation of connexin 36 mediates AII amacrine cell uncoupling.

Publication Date

11-25-2009

Journal

J Neurosci. 2009 November 25; 29(47): 14903–14911.

Abstract

Gap junction proteins form the substrate for electrical coupling between neurons. These electrical synapses are widespread in the CNS and serve a variety of important functions. In the retina, connexin 36 (Cx36) gap junctions couple AII amacrine cells and are a requisite component of the high-sensitivity rod photoreceptor pathway. AII amacrine cell coupling strength is dynamically regulated by background light intensity, and uncoupling is thought to be mediated by dopamine signaling via D(1)-like receptors. One proposed mechanism for this uncoupling involves dopamine-stimulated phosphorylation of Cx36 at regulatory sites, mediated by protein kinase A. Here we provide evidence against this hypothesis and demonstrate a direct relationship between Cx36 phosphorylation and AII amacrine cell coupling strength. Dopamine receptor-driven uncoupling of the AII network results from protein kinase A activation of protein phosphatase 2A and subsequent dephosphorylation of Cx36. Protein phosphatase 1 activity negatively regulates this pathway. We also find that Cx36 gap junctions can exist in widely different phosphorylation states within a single neuron, implying that coupling is controlled at the level of individual gap junctions by locally assembled signaling complexes. This kind of synapse-by-synapse plasticity allows for precise control of neuronal coupling, as well as cell-type-specific responses dependent on the identity of the signaling complexes assembled.

Keywords

Amacrine Cells, Animals, Cell Communication, Connexins, Cyclic AMP-Dependent Protein Kinases, Dopamine, Enzyme Activation, Gap Junctions, Organ Culture Techniques, Phosphorylation, Protein Phosphatase 1, Protein Phosphatase 2, Rabbits, Retina, Signal Transduction, Synaptic Transmission, Vision, Ocular