title: Dopamine-stimulated dephosphorylation of connexin 36 mediates AII amacrine cell uncoupling.
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.
authors: Richard S. Ruiz Department of Ophthalmology, University of Texas Medical School at Houston, Houston, Texas 77030, USA. Wade.Kothmann@gmail.com
authors: W Wade
authors: WW
authors: Kothmann
authors: Stephen C
authors: SC
authors: Massey
authors: John
authors: J
authors: O'Brien
mesh_terms: D025042:Amacrine Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D017630:Connexins / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism* / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009924:Organ Culture Techniques; D010766:Phosphorylation / Q000187:drug effects; D054645:Protein Phosphatase 1 / Q000378:metabolism; D054648:Protein Phosphatase 2 / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits; D012160:Retina / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*; D014785:Vision, Ocular / Q000187:drug effects / Q000502:physiology; D000097004:Gap Junction delta-2 Protein
chemical_list: D017630:Connexins; D017868:Cyclic AMP-Dependent Protein Kinases; D004298:Dopamine; D054645:Protein Phosphatase 1; D054648:Protein Phosphatase 2; D000097004:Gap Junction delta-2 Protein