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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Nedd4-2-dependent regulation of astrocytic Kir4.1 and Connexin43 controls neuronal network activity
The Journal of cell biology, Volume 223, No. 1, Year 2024
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Description
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. Interestingly, our biochemical data demonstrate that missense mutations found in familial epileptic patients produce gain-of-function of the Nedd4-2 gene product. Our data reveal a process of coordinated astrocytic ion channel proteostasis that controls astrocyte function and astrocyte-dependent neuronal network activity and elucidate a potential mechanism by which aberrant Nedd4-2 function leads to epilepsy. © 2023 Altas et al.
Authors & Co-Authors
Altas, Bekir
Germany, Gottingen
Max Planck Institute for Multidisciplinary Sciences
Germany, Gottingen
Georg-august-universität Göttingen
United States, Baltimore
University of Maryland School of Medicine
Rhee, Hongjun
Germany, Gottingen
Max Planck Institute for Multidisciplinary Sciences
Hassan, Mohamed A.
Germany, Gottingen
Max Planck Institute for Multidisciplinary Sciences
Egypt, New Borg el Arab
City of Scientific Research and Technological Applications
Wojcik, Sonja M.
Germany, Gottingen
Max Planck Institute for Multidisciplinary Sciences
Mitkovski, Mišo
Germany, Gottingen
Max Planck Institute for Multidisciplinary Sciences
Urlaub, Henning
Germany, Gottingen
Max Planck Institute for Multidisciplinary Sciences
Germany, Gottingen
Universitätsmedizin Göttingen
Germany, Gottingen
Georg-august-universität Göttingen
Jahn, Olaf
Germany, Gottingen
Max Planck Institute for Multidisciplinary Sciences
Germany, Gottingen
Universitätsmedizin Göttingen
Brose, Nils
Germany, Gottingen
Max Planck Institute for Multidisciplinary Sciences
Statistics
Authors: 8
Affiliations: 10
Identifiers
Doi:
10.1083/jcb.201902050
ISSN:
15408140
Research Areas
Cancer
Genetics And Genomics