1.A.24.1.13
Connexin36, connexin delta2, Cxδ2, GJD2, Cx36 of 321 aas and 4 TMSs. In the developing fetal kidney, cytoplasmic expression of Cx36 is localized to nephrons in different developmental stages, glomerular vessels and collecting ducts. Cx43 is localized to the endothelium of glomerular and peritubular vessels, as well as to the epithelium of the proximal tubules (Ráduly et al. 2019). A reciprocal relationship between Cx36 and seizure-associated neuronal hyperactivityhas been obseerved; thus, Cx36 deficiency contributes to region-specific susceptibility to neuronal hyperactivity, while neuronal hyperactivity-induced downregulation of Cx36 may increase the risk of future epileptic events (Brunal et al. 2020). Cx36 is responsible for signal transmission in electrical synapses by forming interneuronal gap junctions. Lee et al. 2023 determined cryo-electron microscopy structures of Cx36 GJC at 2.2-3.6 Å resolutions, revealing a dynamic equilibrium between its closed and open states. In the closed state, channel pores are obstructed by lipids, while N-terminal TMSs are excluded from the pore. In the open state with pore-lining N-terminal TMSs, the pore is more acidic than those in Cx26 and Cx46/50 GJCs, explaining its strong cation selectivity. The conformational change during channel opening also includes the alpha-to-pi-helix transition of the first transmembrane helix, which weakens the protomer-protomer interaction (Lee et al. 2023).