Dopamine-Stimulated Dephosphorylation of Connexin 36 Mediates AII Amacrine Cell Uncoupling

Authors

W Wade Kothmann
Stephen C Massey
John O'Brien

Language

English

Publication Date

11-25-2009

Journal

The Journal of Neuroscience

DOI

10.1523/JNEUROSCI.3436-09.2009

PMID

19940186

PMCID

PMC2839935

PubMedCentral® Posted Date

11-25-2009

PubMedCentral® Full Text Version

Post-print

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

Published Open-Access

yes

Recommended Citation

W Wade Kothmann, Stephen C Massey, and John O'Brien, "Dopamine-Stimulated Dephosphorylation of Connexin 36 Mediates AII Amacrine Cell Uncoupling" (2009). Faculty, Staff and Student Publications. 224.
https://digitalcommons.library.tmc.edu/uthmed_docs/224