Bekir Altas, Hong-Jun Rhee, Anes Ju, Hugo Cruces Solís, Samir Karaca, Jan Winchenbach, Oykum Kaplan-Arabaci, Manuela Schwark, Mateusz C Ambrozkiewicz, ChungKu Lee, Lena Spieth, Georg L Wieser, Viduth K Chaugule, Irina Majoul, Mohamed A Hassan, Rashi Goel, Sonja M Wojcik, Noriko Koganezawa, Kenji Hanamura, Daniela Rotin, Andrea Pichler, Miso Mitkovski, Livia de Hoz, Alexandros Poulopoulos, Henning Urlaub, Olaf Jahn, Gesine Saher, Nils Brose, JeongSeop Rhee, Hiroshi Kawabe
Nedd4-2 is an E3 ubiquitin ligase in which missense mutation is related to familial epilepsy, indicating its critical role in regulating neuronal network activity. However, Nedd4-2 substrates involved in neuronal network function have yet to be identified. Using mouse lines lacking Nedd4-1 and Nedd4-2, we identified astrocytic channel proteins inwardly rectifying K+ channel 4.1 (Kir4.1) and Connexin43 as Nedd4-2 substrates. We found that the expression of Kir4.1 and Connexin43 is increased upon conditional deletion of Nedd4-2 in astrocytes, leading to an elevation of astrocytic membrane ion permeability and gap junction activity, with a consequent reduction of γ-oscillatory neuronal network activity...
January 1, 2024: Journal of Cell Biology