The DOI matches its Crossref record; 74 of the 74 references it cites were found in a registry or an index.
Calcineurin is associated with the cytoskeleton of cultured neurons and has a role in the acquisition of polarity.
Open accessAbstract
Calcineurin is a calmodulin-dependent serine-threonine phosphatase found in many cell types but most abundant in neurons. To determine its localization in developing neurons, dissociated cultures from embryonic day 15 rat cerebellum were analyzed immunocytochemically after treatment with cytoskeletal-disrupting drugs. During the initial outgrowth of neurites, calcineurin is enriched in growth cones where its localization depends upon the integrity of both microtubules and actin filaments. Treatment with cytochalasin shifts calcineurin from the growth cone to the neurite shaft, and with nocadozole calcineurin translocates to the cell body. Therefore calcineurin is well positioned to mediate interactions between cytoskeletal systems during neurite elongation. By 14 d in culture, when the neurons have developed extensive neuronal contacts and synapses are present, calcineurin is predominantly in the neurite shaft. Incubation of cultured cells with Cyclosporin A or a specific peptide, both of which selectively inhibit calcineurin's phosphatase activity, prevented axonal elongation. Because the microtubule-associated protein tau appears to play a key role in asymmetric neurite elongation, we examined modifications in its phosphorylation state resulting from calcineurin inhibition. In contrast to the normal development of cerebellar macroneurons in which reactivity with the phosphorylation-dependent antibody, tau-1, progressively increases, there was a persistent inhibition of tau-1 reactivity in cells exposed to Cyclosporin A. These findings suggest a role for calcineurin in regulating tau phosphorylation and possibly modulating other steps required for the determination of polarity.
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“In developing cerebellar (Ferreira et al., 1993) and hippocampal (Halpain et al., 1997) neurons, calcineurin is highly concentrated in growth cones, structures that, like spines, contain a dense network of F-actin.”
From Regulation of F-Actin Stability in Dendritic Spines by Glutamate Receptors and Calcineurin (1998) · cites this paper as Ferreira et al., 1993
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“Actin filaments dynamically regulate growth cone motility during axon elongation (Forscher et al., 1992), and the calcineurin antagonist cyclosporin A was shown to inhibit neurite outgrowth in cultured cerebellar neurons (Ferreira et al., 1993).”
From Regulation of F-Actin Stability in Dendritic Spines by Glutamate Receptors and Calcineurin (1998) · cites this paper as Ferreira et al., 1993
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PROTEIN MEASUREMENT WITH THE FOLIN PHENOL REAGENT
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Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes
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Identification of calcineurin as a key signalling enzyme in T-lymphocyte activation
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Saunders, J. J. (2009) · D-Scholarship@Pitt (University of Pittsburgh)
Biological Functions of EF-Hand Ca2+-Binding Proteins
Heizmann, C. W., & Braun, K. A. (1995) · Neuroscience intelligence unit · doi:10.1007/978-3-662-21689-7_5
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Slemmer, J. E. (2005) · EUR Research Repository (Erasmus University Rotterdam)
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Brun, M. M. (2015) · ERA: Education and Research Archive (University of Alberta) · doi:10.7939/r3t14v396
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Long, J.-D., Yao, S.-Y., Wu, W., Zan, G., Wang, Z.-W., Wei, X., Shu, X., Chen, Y., Ju, Y., Chen, J., et al. (2026) · Biological Psychiatry · doi:10.1016/j.biopsych.2026.06.001
Smirnova, I. V., Citron, B. A., Arnold, P. M., & Festoff, B. W. (2001) · Journal of Neurobiology · doi:10.1002/neu.1044
Metadata
- Authors
- Ferreira, A., Kincaid, R., & Kosik, K. S.
- Affiliations
- Harvard University (US)
- Venue
- Molecular Biology of the Cell
- Published
- 1993-12
- Volume
- 4
- Issue
- 12
- Pages
- 1225-1238
- ISSN
- 1059-1524 (ISSN-L)
- 1939-4586
- PMC
- PMC275760
- OpenAlex
- W2092619158
- Cited by
- 110
- References
- 74
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 1 · 2018: 1 · 2017: 2 · 2016: 1 · 2015: 1 · 2013: 3 · 2012: 2
- FWCI
- 3.01
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Biology of the Cell (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ag006601-13, 5r01ns029031-09)
- National Institute on Aging (AG 06601)
- National Institute of Neurological Disorders and Stroke (NS29031)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- calcineurin, neuronal polarity, neurite outgrowth, growth cones, microtubules, F-actin, tau phosphorylation, cyclosporine, cerebellar neurons, axon elongation
- MeSH terms
- Animals, Calmodulin-Binding Proteins, Cell Differentiation, Cells, Cultured, Cerebellum, Cytoskeleton, Actin Cytoskeleton, Microtubules, Nerve Tissue Proteins, Neurons, Phosphoprotein Phosphatases, Phosphorylation, Protein Processing, Post-Translational, Cytochalasin D, Nocodazole, Neurites, Cyclosporine, Cell Polarity, tau Proteins, Calcineurin, Rats
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