| First Author | Tapia M | Year | 2013 |
| Journal | Cell Mol Life Sci | Volume | 70 |
| Issue | 1 | Pages | 105-20 |
| PubMed ID | 22763697 | Mgi Jnum | J:315116 |
| Mgi Id | MGI:6829867 | Doi | 10.1007/s00018-012-1059-5 |
| Citation | Tapia M, et al. (2013) GSK3 and beta-catenin determines functional expression of sodium channels at the axon initial segment. Cell Mol Life Sci 70(1):105-20 |
| abstractText | Neuronal action potentials are generated through voltage-gated sodium channels, which are tethered by ankyrinG at the membrane of the axon initial segment (AIS). Despite the importance of the AIS in the control of neuronal excitability, the cellular and molecular mechanisms regulating sodium channel expression at the AIS remain elusive. Our results show that GSK3alpha/beta and beta-catenin phosphorylated by GSK3 (S33/37/T41) are localized at the AIS and are new components of this essential neuronal domain. Pharmacological inhibition of GSK3 or beta-catenin knockdown with shRNAs decreased the levels of phosphorylated-beta-catenin, ankyrinG, and voltage-gated sodium channels at the AIS, both "in vitro" and "in vivo", therefore diminishing neuronal excitability as evaluated via sodium current amplitude and action potential number. Thus, our results suggest a mechanism for the modulation of neuronal excitability through the control of sodium channel density by GSK3 and beta-catenin at the AIS. |
