Gap junction channel gating modulated through protein phosphorylation

Abstract

As a ubiquitous post-translation modification process, protein phosphorylation has proven to be a key mechanism in regulating the function of several membrane proteins, including transporters and channels. Connexins, pannexins, and innexins are protein families that form gap junction channels essential for intercellular communication. Connexins have been intensely studied, and most of their isoforms are known to be phosphorylated by protein kinases that lead to modifications in tyrosine, serine, and threonine residues, which have been reported to affect, in one way or another, intercellular communication. Despite the abundant reports on changes in intercellular communication due to the activation or inactivation of numerous kinases, the molecular mechanisms by which phosphorylation alters channel gating properties have not been elucidated completely. Hence, this chapter will cover some of the current, relevant research that attempt to explain how phosphorylation triggers and/or modulates gap junction channel gating.

Nongenomic glucocorticoid receptor action regulates gap junction intercellular communication and neural progenitor cell proliferation

“…A reduction in GJIC may result from phosphorylation (15,20) of connexins and/or from a change in connexin gene expression. GC induces connexin-26 (Cx26) expression in cultured rat hepatocytes (16).…”

Interaction between Connexin50 and Mitogen-activated Protein Kinase Signaling in Lens Homeostasis

“…Alternatively, it may have been because of an augmented rate of channel assembly. All of these parameters can be influenced by phosphorylation of connexin subunits (Moreno and Lau, 2007) and could potentially result from Cx50 being phosphorylated either directly by MAPKs or indirectly via other kinases activated by the MAPK pathway. Future investigation of these parameters may help explain why Cx50 junctional conductance was specifically increased compared with that mediated by Cx46.…”

Electrical synapses between AII amacrine cells in the retina: Function and modulation

“…The gap junction coupling between neurons (and many other cells) is mediated by specialized channel proteins termed connexins (reviewed by Söhl et al, 2005) where post-translational modification by phosphorylation can modulate important functional properties (reviewed by Moreno and Lau, 2007). As with other areas of the CNS, progress in our understanding of electrical synaptic transmission in the retina is to a large extent hampered by the difficulties associated with investigating the structure and function of intact neural circuits under natural conditions.…”