Structural basis of connexin-36 gap junction channel inhibition
Xinyue Ding, Simone Aureli, Anand Vaithia, Pia Lavriha, Dina Schuster, Basavraj Khanppnavar, Xiaodan Li, Thorsten B. Blum, Paola Picotti, Francesco Luigi Gervasio, Volodymyr M. Korkhov
Abstract
Connexins (Cxs) assemble as hexameric hemichannels (HCs) that reach the cellular surface and dock with their counterparts on the neighboring cells, forming the gap junction channels (GJCs) and coupling cells metabolically and electrically. Pancreatic Cx36 plays a crucial role in insulin secretion 1 , whereas in the brain Cx36 is involved in neuronal synchronization 2 . Dysregulation of Cx36 is associated with epilepsy, traumatic brain injury, and ischemia 3 , and elevated gap junction coupling in these conditions contributes to neuronal death. The development of selective inhibitors of Cx36 could be of therapeutic value. Although a structure of Cx36 has been determined recently 4 , it remains unclear how drugs inhibit the Cx36 and other Cx channels.