| First Author | Kim JE | Year | 2017 |
| Journal | Front Mol Neurosci | Volume | 10 |
| Pages | 303 | PubMed ID | 28993724 |
| Mgi Jnum | J:294856 | Mgi Id | MGI:6458863 |
| Doi | 10.3389/fnmol.2017.00303 | Citation | Kim JE, et al. (2017) PLPP/CIN Regulates Seizure Activity by the Differential Modulation of Calsenilin Binding to GluN1 and Kv4.2 in Mice. Front Mol Neurosci 10:303 |
| abstractText | Calsenilin (CSEN) binds to Kv4.2 (an A-type K(+) channel) as well as N-methyl-D-aspartate receptor (NMDAR), and modulates their activities. However, the regulatory mechanisms for CSEN-binding to Kv4.2 or NMDAR remain elusive. Here, we demonstrate the novel role of pyridoxal-5'-phosphate phosphatase/chronophin (PLPP/CIN), one of the cofilin-mediated F-actin regulators, in the CSEN binding to Kv4.2 or GluN1 (an NMDAR subunit). PLPP/CIN dephosphorylated CSEN in competition with casein kinase 1, independent of cofilin dephosphorylation. As compared to wild-type mice, PLPP/CIN transgenic (PLPP/CIN(Tg)) mice showed the enhancement of Kv4.2-CSEN binding, but the reduction in CSEN-GluN1 binding. In addition, PLPP/CIN(Tg) mice exhibited the higher intensity (severity), duration and progression of seizures, but the longer latency of seizure on-set in response to kainic acid. PLPP/CIN knockout mice reversed these phenomena. Therefore, we suggest that PLPP/CIN-mediated CSEN dephosphorylation may play an important role in the functional coupling of NMDAR and Kv4.2, which regulates the neuronal excitability. |
