AI Article Synopsis
- Epilepsy, a condition affecting over 65 million people globally, lacks comprehensive understanding, prompting research into its underlying mechanisms.
- The study reveals that the absence of polycystin-L (PCL), a protein that influences neuronal excitability, leads to increased seizures in mice by impacting the β2-adrenergic receptor (β2AR) and reducing key chemical signals in the brain.
- The findings suggest that a specific ciliary protein complex is crucial for regulating brain cell activity and could provide new insights for addressing epilepsy.
Article 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 β2-adrenergic receptor (β2AR) and co-localizes with β2AR on the primary cilia of neurons in the brain. Pkdl deficiency leads to the loss of β2AR 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4731019 | PMC |
| http://dx.doi.org/10.1093/hmg/ddv484 | DOI Listing |
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