AnkyrinG is required for maintenance of the axon initial segment and neuronal polarity
Open accessAbstract
The axon initial segment (AIS) functions as both a physiological and physical bridge between somatodendritic and axonal domains. Given its unique molecular composition, location, and physiology, the AIS is thought to maintain neuronal polarity. To identify the molecular basis of this AIS property, we used adenovirus-mediated RNA interference to silence AIS protein expression in polarized neurons. Some AIS proteins are remarkably stable with half-lives of at least 2 wk. However, silencing the expression of the cytoskeletal scaffold ankyrinG (ankG) dismantles the AIS and causes axons to acquire the molecular characteristics of dendrites. Both cytoplasmic- and membrane-associated proteins, which are normally restricted to somatodendritic domains, redistribute into the former axon. Furthermore, spines and postsynaptic densities of excitatory synapses assemble on former axons. Our results demonstrate that the loss of ankG causes axons to acquire the molecular characteristics of dendrites; thus, ankG is required for the maintenance of neuronal polarity and molecular organization of the AIS.
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Loss of the ankyrinG-based AIS has been shown to disrupt the maintenance of neuronal polarity and to allow the axon to acquire molecular features of dendrites, such as axonal MAP2 and postsynaptic proteins.
“Loss of the ankyrinG-based AIS has been shown to disrupt the maintenance of neuronal polarity and to allow the axon to acquire molecular features of dendrites, such as axonal MAP2 (30) and postsynaptic proteins (31).”
From Active transport by cytoplasmic dynein sustains dendritic MAP2 localization in developing neurons (2026) · cites this paper as [30]
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The axon initial segment and the maintenance of neuronal polarity
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“AIS length was assessed by immunostaining for the scaffold protein Ankyrin-G (Hedstrom et al., 2008; Ogawa & Rasband, 2008) ( Figure 5E ).”
Active transport by cytoplasmic dynein sustains dendritic MAP2 localization in developing neurons
Yonemura, Y., Sakai, Y., Nakata, R., Hagita-Tatsumoto, A., Miyasaka, T., & Misonou, H. (2026) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2026.113407
- Authors
- Hedstrom, K. L., Ogawa, Y., & Rasband, M. N.
- Affiliations
- UConn Health (US)
- Baylor College of Medicine (US)
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2008-11-10
- Volume
- 183
- Issue
- 4
- Pages
- 635-640
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2582894
- OpenAlex
- W1989809732
- Cited by
- 371
- References
- 3
- Citations by year
- 2026: 13 · 2025: 12 · 2024: 19 · 2023: 14 · 2022: 25 · 2021: 18 · 2020: 20 · 2019: 17 · 2018: 19 · 2017: 30 · 2016: 27 · 2015: 28 · 2014: 23 · 2013: 24 · 2012: 27
- FWCI
- 7.93
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS 044916, R01NS044916, R37NS044916)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- ankyrin-G, axon initial segment, neuronal polarity, axon-dendrite polarity, axon maintenance, dendritic spine formation, postsynaptic density, excitatory synapses, protein redistribution
- MeSH terms
- Adenoviridae, Animals, Axons, Cells, Cultured, Dendrites, Gene Expression Regulation, Nerve Tissue Proteins, Time Factors, Cell Polarity, Ankyrins, RNA Interference, Mice
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