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β spectrin-dependent and domain specific mechanisms for Na + channel clustering.
- Source :
-
ELife [Elife] 2020 May 19; Vol. 9. Date of Electronic Publication: 2020 May 19. - Publication Year :
- 2020
-
Abstract
- Previously, we showed that a hierarchy of spectrin cytoskeletal proteins maintains nodal Na <superscript>+</superscript> channels (Liu et al., 2020). Here, using mice lacking β1, β4, or β1/β4 spectrins, we show this hierarchy does not function at axon initial segments (AIS). Although β1 spectrin, together with AnkyrinR (AnkR), compensates for loss of nodal β4 spectrin, it cannot compensate at AIS. We show AnkR lacks the domain necessary for AIS localization. Whereas loss of β4 spectrin causes motor impairment and disrupts AIS, loss of β1 spectrin has no discernable effect on central nervous system structure or function. However, mice lacking both neuronal β1 and β4 spectrin show exacerbated nervous system dysfunction compared to mice lacking β1 or β4 spectrin alone, including profound disruption of AIS Na <superscript>+</superscript> channel clustering, progressive loss of nodal Na <superscript>+</superscript> channels, and seizures. These results further define the important role of AIS and nodal spectrins for nervous system function.<br />Competing Interests: CL, RS, TH, MS, PM, TH, JN, MR No competing interests declared<br /> (© 2020, Liu et al.)
- Subjects :
- Animals
Ankyrins metabolism
Behavior, Animal
Carrier Proteins genetics
Cells, Cultured
Female
Hippocampus physiopathology
Male
Mice, 129 Strain
Mice, Inbred C57BL
Mice, Knockout
Microfilament Proteins deficiency
Microfilament Proteins genetics
Motor Activity
Protein Domains
Rotarod Performance Test
Seizures genetics
Seizures metabolism
Seizures physiopathology
Spectrin deficiency
Spectrin genetics
Axon Initial Segment metabolism
Carrier Proteins metabolism
Hippocampus metabolism
Microfilament Proteins metabolism
Spectrin metabolism
Voltage-Gated Sodium Channels metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2050-084X
- Volume :
- 9
- Database :
- MEDLINE
- Journal :
- ELife
- Publication Type :
- Academic Journal
- Accession number :
- 32425157
- Full Text :
- https://doi.org/10.7554/eLife.56629