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1دورية أكاديمية
المؤلفون: Altas, B., Rhee, H., Ju, A., Solis, H., Karaca, S., Winchenbach, J., Kaplan-Arabaci, O., Schwark, M., Ambrozkiewicz, M., Lee, C., Spieth, L., Wieser, G., Chaugule, V., Majoul, I., Hassan, M., Goel, R., Wojcik, S., Koganezawa, N., Hanamura, K., Rotin, D., Pichler, A., Mitkovski, M., de Hoz, L., Poulopoulos, A., Urlaub, H., Jahn, O., Saher, G., Brose, N., Rhee, J., Kawabe, H.
المصدر: Journal of Cell Biology
الوصف: 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.
وصف الملف: application/pdf
العلاقة: http://hdl.handle.net/21.11116/0000-000E-7957-9Test; http://hdl.handle.net/21.11116/0000-000E-7959-7Test
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2دورية أكاديمية
المؤلفون: Altas, B., Rhee, H., Ju, A., Solís, H., Karaca, S., Winchenbach, J., Kaplan-Arabaci, O., Schwark, M., Ambrozkiewicz, M., Lee, C., Spieth, L., Wieser, G., Chaugule, V., Majoul, I., Hassan, M., Goel, R., Wojcik, S., Koganezawa, N., Hanamura, K., Rotin, D., Pichler, A., Mitkovski, M., de Hoz, L., Poulopoulos, A., Urlaub, H., Jahn, O., Saher, G., Brose, N., Rhee, J., Kawabe, H.
المصدر: Journal of Cell Biology
الوصف: 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.
وصف الملف: application/pdf
العلاقة: http://hdl.handle.net/21.11116/0000-000D-FEE5-3Test; http://hdl.handle.net/21.11116/0000-000D-FEE7-1Test
