PLPP/CIN Regulates Seizure Activity by the Differential Modulation of Calsenilin Binding to GluN1 and Kv4.2 in Mice.

ABSTRACT: 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 (severi

SUBMITTER: Kim JE 

PROVIDER: S-EPMC5622162 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature