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

Calsenilin (CSEN) binds to Kv4.2 (an A-type K channel) as well as -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...

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Published in:Frontiers in molecular neuroscience 2017-09, Vol.10, p.303-303
Main Authors: Kim, Ji-Eun, Hyun, Hye-Won, Min, Su-Ji, Lee, Duk-Shin, Jeon, A Ran, Kim, Min Ju, Kang, Tae-Cheon
Format: Article
Language:English
Subjects:
Actin
Casein
Casein kinase I
Cofilin
Convulsions & seizures
dendritic spine
Dephosphorylation
DREAM
Epilepsy
Excitability
F-actin
Gene expression
Glutamic acid receptors
Kainic acid
KChIP3
Kinases
Latency
N-Methyl-D-aspartic acid receptors
Neuroscience
Neurosciences
Phosphatase
Potassium
Potassium channels
Potassium channels (voltage-gated)
Proteins
Seizures
Transgenic mice
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Summary:Calsenilin (CSEN) binds to Kv4.2 (an A-type K channel) as well as -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 ) mice showed the enhancement of Kv4.2-CSEN binding, but the reduction in CSEN-GluN1 binding. In addition, PLPP/CIN 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.
ISSN:1662-5099
1662-5099
DOI:10.3389/fnmol.2017.00303