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Cited by 57Alzheimer's disease research and treatmentsProtein Kinase Regulation and GTPase SignalingNeuroblastoma Research and Treatments

Regulation of protein phosphatase 2A methylation by LCMT1 and PME‐1 plays a critical role in differentiation of neuroblastoma cells

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Sontag, Jean‐Marie, Nunbhakdi‐Craig, Viyada, Mitterhuber, Martina, Ogris, Egon, Sontag, Estelle·2010·Journal of Neurochemistry
DOI 10.1111/j.1471-4159.2010.07049.xPMC PMC3057931
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Abstract

J. Neurochem. (2010) 115, 1455–1465. Neuritic alterations are a major feature of many neurodegenerative disorders. Methylation of protein phosphatase 2A (PP2A) catalytic C subunit by the leucine carboxyl methyltransferase (LCMT1), and demethylation by the protein phosphatase methylesterase 1, is a critical PP2A regulatory mechanism. It modulates the formation of PP2A holoenzymes containing the Bα subunit, which dephosphorylate key neuronal cytoskeletal proteins, including tau. Significantly, we have reported that LCMT1, methylated C and Bα expression levels are down‐regulated in Alzheimer disease‐affected brain regions. In this study, we show that enhanced expression of LCMT1 in cultured N2a neuroblastoma cells, which increases endogenous methylated C and Bα levels, induces changes in F‐actin organization. It promotes serum‐independent neuritogenesis and development of extended tau‐positive processes upon N2a cell differentiation. These stimulatory effects can be abrogated by LCMT1 knockdown and S‐adenosylhomocysteine, an inhibitor of methylation reactions. Expression of protein phosphatase methylesterase 1 and the methylation‐site L309Δ C subunit mutant, which decrease intracellular methylated C and Bα levels, block N2a cell differentiation and LCMT1‐mediated neurite formation. Lastly, inducible and non‐inducible knockdown of Bα in N2a cells inhibit process outgrowth. Altogether, our results establish a novel mechanistic link between PP2A methylation and development of neurite‐like processes.

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  • Tau colocalizes with actin in differentiating PC12 cells, N2a cells and in the postsynaptic compartments of mature neurons.

    “Tau colocalizes with actin in differentiating PC12 cells68, N2a cells69 and in the postsynaptic compartments of mature neurons70.”

    From Multivalent cross-linking of actin filaments and microtubules through the microtubule-associated protein Tau (2017) · cites this paper as [69]

    The Results (page unavailable) report tau-positive processes and altered F-actin organization in differentiating N2a cells. They do not report that tau and actin colocalize; the cited paper supports their presence in these cells, but not the specific spatial relationship attributed to it. Citation 69 is attached only to the N2a-cell portion of the sentence. (LLM, conf=0.84)

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Research works printed but not linked: 37

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Cited by

Sorted by citations

Authors
Sontag, J., Nunbhakdi‐Craig, V., Mitterhuber, M., Ogris, E., & Sontag, E.
Affiliations
  • University of Newcastle Australia (AU)
  • The University of Texas Southwestern Medical Center (US)
  • Max Perutz Labs (AT)
ORCID
Venue
Journal of Neurochemistry
Publisher
Wiley
Published
2010-11-04
Volume
115
Issue
6
Pages
1455-1465
ISSN
  • 0022-3042 (ISSN-L)
  • 1471-4159
DOI
10.1111/j.1471-4159.2010.07049.x
PMC
PMC3057931
OpenAlex
W1494691627
Cited by
57
References
9
Citations by year
2026: 2 · 2024: 2 · 2023: 1 · 2022: 5 · 2021: 4 · 2020: 5 · 2019: 2 · 2018: 4 · 2017: 4 · 2016: 6 · 2015: 6 · 2014: 5 · 2013: 3 · 2012: 3
FWCI
2.23
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Journal of Neurochemistry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Newcastle University
  • National Institutes of Health
  • National Institute on Aging (AG 18883, R56AG018883, R01AG018883)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Health Sciences › Medicine › Neurology › Neuroblastoma Research and Treatments
Keywords
protein phosphatase 2A, PP2A holoenzyme, neurite outgrowth, neuroblastoma cell differentiation, F-actin organization, tau protein, S-adenosylhomocysteine, Alzheimer's disease, neuronal cytoskeleton
MeSH terms
Animals, Carboxylic Ester Hydrolases, Cell Differentiation, Cells, Cultured, Neuroblastoma, Protein O-Methyltransferase, Neurites, DNA Methylation, Catalytic Domain, Cell Line, Tumor, Mice, Protein Phosphatase 2, Gene Knockdown Techniques

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