The two faces of pannexins: new roles in inflammation and repair

Abstract

Helen P Makarenkova,1 Sameer B Shah,2,3 Valery I Shestopalov4–6 1Department of Molecular Medicine, Scripps Research Institute, 2Departments of Orthopaedic Surgery and Bioengineering, University of California, 3Research Division, Veterans Affairs San Diego Healthcare System, San Diego, CA, 4Bascom Eye Institute, Department of Ophthalmology, University of Miami, Miami, FL, USA; 5Vavilov Institute for General Genetics, Russian Academy of Sciences, 6Kharkevich Institute for Information Transmission Problems, Russian Academy of Sciences, Moscow, Russia Abstract: Pannexins belong to a family of ATP-release channels expressed in almost all cell types. An increasing body of literature on pannexins suggests that these channels play dual and sometimes contradictory roles, contributing to normal cell function, as well as to the pathological progression of disease. In this review, we summarize our understanding of pannexin “protective” and “harmful” functions in inflammation, regeneration and mechanical signaling. We also suggest a possible basis for pannexin’s dual roles, related to extracellular ATP and K+ levels and the activation of various types of P2 receptors that are associated with pannexin. Finally, we speculate upon therapeutic strategies related to pannexin using eyes, lacrimal glands, and peripheral nerves as examples of interesting therapeutic targets. Keywords: pannexin, Panx1, ATP, purinergic signaling, inflammation, regeneration

Keywords

• Pannexin
• Panx1
• ATP
• purinergic signaling
• inflammation
• regeneration.