Activity-regulated micro-exon splicing programs underlie late-onset plasticity at the axon initial segment Article Swipe
Mohamed Darwish
,
Satoko Suzuki
,
Yuki Ogawa
,
Akinori Takase
,
Masami Tanaka
,
Yoko Iijima
,
Yuji Sato
,
Mariko Suzuki
,
Yumi Kanegae
,
Chisa Okada
,
Masayuki Takana
,
Hirotaka-James Okano
,
Hiroshi Kuba
,
Takatoshi Iijima
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1101/2023.10.29.564567
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1101/2023.10.29.564567
The axon initial segment (AIS) is a specialized neuronal compartment located at the proximal end of axons and initiates action potentials. AIS undergoes plastic changes with aging, disease, and activity levels; however, the molecular mechanisms underlying their plasticity remain unclear. We discovered that depolarization induces diffuse elongation of the AIS in cerebellar granule cells over the span of days via the Ca 2+ -dependent ERK/MAP kinase pathway. These structural changes were accompanied by a decrease in voltage-gated Na + channel density, resulting in a homeostatic attenuation in neuronal excitability. Notably, we found that the late-onset AIS plasticity is associated with depolarization-induced alternative splicing of smaller exons (<100 nt) of transcripts encoding AIS-enriched proteins. In addition, depolarization-induced the skipping of the 53-nt exon19 from the transcript of the splicing protein Rbfox1. CRISPR-mediated removal of exon 19 from Rbfox1 promoted its nuclear localization and sequentially induced a series of downstream micro-exon splicing changes in several AIS proteins, recapitulating cerebellar AIS plasticity. In a Rbfox1-independent mechanism, depolarization-induced insertion of the developmentally regulated micro-exon 34 into the key AIS scaffolding protein Ankyrin G (AnkG). The constitutive insertion of exon 34 into AnkG disrupted its interaction with the AIS cytoskeletal protein βIV spectrin and induced plastic changes in the AIS. Our findings provide fundamental mechanistic insights into the activity-mediated late-onset plasticity of AIS, highlighting the power of micro-scale splicing events in the homeostatic regulation of axonal remodeling.
Related Topics
Concepts
Biology
Exon
Alternative splicing
RNA splicing
Cell biology
Depolarization
Neuroscience
Genetics
Gene
Endocrinology
RNA
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2023.10.29.564567
- https://www.biorxiv.org/content/biorxiv/early/2023/10/30/2023.10.29.564567.full.pdf
- OA Status
- green
- Cited By
- 1
- References
- 47
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4388102533
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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- DOI
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https://doi.org/10.1101/2023.10.29.564567Digital Object Identifier
- Title
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Activity-regulated micro-exon splicing programs underlie late-onset plasticity at the axon initial segmentWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2023Year of publication
- Publication date
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2023-10-30Full publication date if available
- Authors
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Mohamed Darwish, Satoko Suzuki, Yuki Ogawa, Akinori Takase, Masami Tanaka, Yoko Iijima, Yuji Sato, Mariko Suzuki, Yumi Kanegae, Chisa Okada, Masayuki Takana, Hirotaka-James Okano, Hiroshi Kuba, Takatoshi IijimaList of authors in order
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https://doi.org/10.1101/2023.10.29.564567Publisher landing page
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https://www.biorxiv.org/content/biorxiv/early/2023/10/30/2023.10.29.564567.full.pdfDirect link to full text PDF
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YesWhether a free full text is available
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greenOpen access status per OpenAlex
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https://www.biorxiv.org/content/biorxiv/early/2023/10/30/2023.10.29.564567.full.pdfDirect OA link when available
- Concepts
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Biology, Exon, Alternative splicing, RNA splicing, Cell biology, Depolarization, Neuroscience, Genetics, Gene, Endocrinology, RNATop concepts (fields/topics) attached by OpenAlex
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1Total citation count in OpenAlex
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2025: 1Per-year citation counts (last 5 years)
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47Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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