Regulation of pannexin channels by post-translational modifications.
The large-pore channels formed by the pannexin family of proteins have been implicated in many physiological and pathophysiological functions, mainly through their ATP release function. However, a tight regulation of channel opening is necessary to modulate their function in vivo. Post-translational modifications have been postulated as some of the regulating mechanisms for Panx1, while Panx2 and Panx3 have not been as well characterized. Positive regulators include caspase cleavage to open Panx1 channels in apoptotic cells, and activation by Src family kinases via ionotropic receptors in neurons and macrophages. S-nitrosylation of cysteines has been shown to both inhibit and activate the Panx1 channel in different cell types. All three pannexins are N-glycosylated but to different levels of modification. Their diverse glycosylation appears to regulate cellular localization, intermixing, and may restrict their ability to function as inter-cellular channels. It is clear that our understanding of pannexin post-translational modification and their role in channel function regulation is still in its infancy even a decade after their discovery.
Department of Anatomy and Cell Biology, University of Western Ontario, London, ON N6A5C1, Canada. Electronic address: spenuela@uwo.ca.
Silvia
S
Penuela
Department of Physiology and Pharmacology, University of Western Ontario, London, ON N6A5C1, Canada.
Jamie
J
Simek
Hotchkiss Brain Institute and Department of Cell Biology and Anatomy, University of Calgary, Calgary, AB T2N 4N1, Canada.
Roger J
RJ
Thompson
D000818:Animals; D020169:Caspases / Q000378:metabolism; D017630:Connexins / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D009589:Nitrogen Oxides / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D059748:Proteolysis
D017630:Connexins; D009589:Nitrogen Oxides; D020169:Caspases
Channel; Pannexin; Panx1; Panx2; Panx3; Post-translational modifications