| First Author | Liu CH | Year | 2020 |
| Journal | Elife | Volume | 9 |
| PubMed ID | 32425157 | Mgi Jnum | J:290601 |
| Mgi Id | MGI:6442616 | Doi | 10.7554/eLife.56629 |
| Citation | Liu CH, et al. (2020) beta spectrin-dependent and domain specific mechanisms for Na(+) channel clustering. Elife 9:e56629 |
| abstractText | Previously, we showed that a hierarchy of spectrin cytoskeletal proteins maintains nodal Na(+) channels (Liu et al., 2020). Here, using mice lacking beta1, beta4, or beta1/beta4 spectrins, we show this hierarchy does not function at axon initial segments (AIS). Although beta1 spectrin, together with AnkyrinR (AnkR), compensates for loss of nodal beta4 spectrin, it cannot compensate at AIS. We show AnkR lacks the domain necessary for AIS localization. Whereas loss of beta4 spectrin causes motor impairment and disrupts AIS, loss of beta1 spectrin has no discernable effect on central nervous system structure or function. However, mice lacking both neuronal beta1 and beta4 spectrin show exacerbated nervous system dysfunction compared to mice lacking beta1 or beta4 spectrin alone, including profound disruption of AIS Na(+) channel clustering, progressive loss of nodal Na(+) channels, and seizures. These results further define the important role of AIS and nodal spectrins for nervous system function. |
