Unknown

Dataset Information

0

Disruption of polycystin-L causes hippocampal and thalamocortical hyperexcitability.


ABSTRACT: Epilepsy or seizure disorder is among the least understood chronic medical conditions affecting over 65 million people worldwide. Here, we show that disruption of the polycystic kidney disease 2-like 1 (Pkd2l1 or Pkdl), encoding polycystin-L (PCL), a non-selective cation channel, increases neuronal excitability and the susceptibility to pentylenetetrazol-induced seizure in mice. PCL interacts with ?2-adrenergic receptor (?2AR) and co-localizes with ?2AR on the primary cilia of neurons in the brain. Pkdl deficiency leads to the loss of ?2AR on neuronal cilia, which is accompanied with a remarkable reduction in cAMP levels in the central nervous system (CNS). The reduction of cAMP levels is associated with a reduction in the activation of cAMP response element-binding protein, but not the activation of Ca(2+)/calmodulin-dependent protein kinase II, Akt or mitogen-activated protein kinases. Our data, thus, indicate for the first time that a ciliary protein complex is required for the control of neuronal excitability in the CNS.

SUBMITTER: Yao G 

PROVIDER: S-EPMC4731019 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

altmetric image

Publications

Disruption of polycystin-L causes hippocampal and thalamocortical hyperexcitability.

Yao Gang G   Luo Chong C   Harvey Michael M   Wu Maoqing M   Schreiber Taylor H TH   Du Yanjun Y   Basora Nuria N   Su Xuefeng X   Contreras Diego D   Zhou Jing J  

Human molecular genetics 20151126 3


Epilepsy or seizure disorder is among the least understood chronic medical conditions affecting over 65 million people worldwide. Here, we show that disruption of the polycystic kidney disease 2-like 1 (Pkd2l1 or Pkdl), encoding polycystin-L (PCL), a non-selective cation channel, increases neuronal excitability and the susceptibility to pentylenetetrazol-induced seizure in mice. PCL interacts with β2-adrenergic receptor (β2AR) and co-localizes with β2AR on the primary cilia of neurons in the bra  ...[more]

Similar Datasets

| S-EPMC2928878 | biostudies-literature
| S-EPMC9095835 | biostudies-literature
| S-EPMC2882519 | biostudies-literature
| S-EPMC5156834 | biostudies-literature
| S-EPMC6057643 | biostudies-literature
| S-EPMC6347466 | biostudies-literature
| S-EPMC5097044 | biostudies-literature
| S-EPMC4277673 | biostudies-literature
| S-EPMC2722891 | biostudies-other
| S-EPMC10371821 | biostudies-literature