| First Author | Yao G | Year | 2016 |
| Journal | Hum Mol Genet | Volume | 25 |
| Issue | 3 | Pages | 448-58 |
| PubMed ID | 26612203 | Mgi Jnum | J:229324 |
| Mgi Id | MGI:5751629 | Doi | 10.1093/hmg/ddv484 |
| Citation | Yao G, et al. (2016) Disruption of polycystin-L causes hippocampal and thalamocortical hyperexcitability. Hum Mol Genet 25(3):448-58 |
| abstractText | 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 beta2-adrenergic receptor (beta2AR) and co-localizes with beta2AR on the primary cilia of neurons in the brain. Pkdl deficiency leads to the loss of beta2AR 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. |
