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Astn2, A Novel Member of the Astrotactin Gene Family, Regulates the Trafficking of ASTN1 during Glial-Guided Neuronal Migration
Open accessAbstract
Glial-guided neuronal migration is a key step in the development of laminar architecture of cortical regions of the mammalian brain. We previously reported that neuronal protein astrotactin (ASTN1) functions as a neuron-glial ligand during CNS glial-guided migration. Here, we identify a new Astn family member, Astn2, that is expressed at high levels in migrating, cerebellar granule neurons, along with Astn1, at developmental stages when glial-guided migration is ongoing. Biochemical and flow cytometry experiments show that ASTN2 forms a complex with ASTN1 and regulates surface expression of ASTN1. Live imaging of Venus-tagged ASTN1 in migrating cerebellar granule cells reveals the intracellular trafficking of ASTN1-Venus, with ASTN1-Venus accumulating in the forward aspect of the leading process where new sites of adhesion will form. Treatment of migrating neurons with Dynasore, a soluble noncompetitive inhibitor of Dynamin, rapidly arrests the migration of immature granule cells in a reversible manner, suggesting the critical importance of receptor trafficking to neuronal locomotion along Bergmann glial fibers in the developing cerebellum. Together, these findings suggest that ASTN2 regulates the levels of ASTN1 in the plasma membrane and that the release of neuronal adhesions to the glial fiber during neuronal locomotion involves the intracellular trafficking of ASTN1.
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“A further gene involved in cell adhesion, astrotactin 2 (ASTN2), which we found to be putatively associated with depression is also involved in ADHD aetiology 32 and plays a role in neuronal development in the brain 33.”
From Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions (2019) · cites this paper as [33]
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“ASTN2 interacts with ASTN1, regulating its expression, thereby playing a role in neuronal-glial adhesion during migration [55].”
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Metadata
- Authors
- Wilson, P. M., Fryer, R. H., Fang, Y., & Hatten, M. E.
- Affiliations
- Rockefeller University (US)
- Corresponding author
- Hatten, M. E.
- Venue
- Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2010-06-23
- Volume
- 30
- Issue
- 25
- Pages
- 8529-8540
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2905051
- OpenAlex
- W1996840895
- Cited by
- 169
- References
- 49
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 13 · 2023: 10 · 2022: 15 · 2021: 14 · 2020: 10 · 2019: 8 · 2018: 8 · 2017: 17 · 2016: 9 · 2015: 8 · 2014: 12 · 2013: 13 · 2012: 11
- FWCI
- 3.24
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (T32GM007524, GM07524)
- National Institute of Neurological Disorders and Stroke (R01NS015429, R01NS051778)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- ASTN2, cerebellar granule cells, receptor trafficking, dynamin, dynasore, leading process, cortical lamination, protein complex formation
- MeSH terms
- Animals, Cell Line, Cell Movement, Cells, Cultured, Cerebellum, Flow Cytometry, Glycoproteins, Hydrazones, Immunohistochemistry, Nerve Tissue Proteins, Neuroglia, Neurons, Transfection, Blotting, Northern, In Situ Hybridization, Microscopy, Confocal, Dynamins, Mice
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