Fig. 8: Effect of neuronal activity in response to AMPA and the hypothesized role of PCPP/CIN-mediated GluA1 ubiquitination. | Cell Death & Disease

Fig. 8: Effect of neuronal activity in response to AMPA and the hypothesized role of PCPP/CIN-mediated GluA1 ubiquitination.

From: PLPP/CIN-mediated NEDD4-2 S448 dephosphorylation regulates neuronal excitability via GluA1 ubiquitination

Fig. 8

a, b Effects of PLPP/CIN overexpression on neuronal activity in response to AMPA. PLPP/CINTg mice demonstrate the increased neuronal activity in response to AMPA. a Representative EEG traces and frequency-power spectral temporal maps in response to AMPA. b Quantification of total EEG power in response to AMPA (mean ± S.E.M.; p < 0.05 vs. WT animals; n = 7, respectively). c Scheme of inhibitory role of PLPP/CIN in NEDD4-2-mediated GluA1 ubiquitination. Protein kinases including SGK1 phosphorylate NEDD4-2 S342 and S448 sites, which facilitate its binding to and ubiquitination of GluA1. However, PLPP/CIN dephosphorylates NEDD4-2 S448 site, which leads to ubiquitination of NEDD4-2 and subsequently inhibits GluA1 ubiquitination, independent of SGK1 activity. These PLPP/CIN-mediated functional couplings of NEDD4-2 and GluA1 increase seizure intensity and its progression

Back to article page