Notch activation induces neurite remodeling and functional modifications in SH-SY5Y neuronal cells

Autor: Francesco Napolitano, Daniela Uberti, Giuseppina Minopoli, Federica Santoro, Tommaso Russo, Maurizio Memo, Nicola Zambrano, Giulia Ferrari-Toninelli, Sara Anna Bonini, Maria Stante
Přispěvatelé: Ferrari Toninelli, G, Bonini, Sa, Uberti, D, Napolitano, F, Stante, Maria, Santoro, F, Minopoli, Giuseppina, Zambrano, Nicola, Russo, Tommaso, Memo, M.
Rok vydání: 2009
Předmět:
NA release
SH-SY5Y
Time Factors
Neurite
Microtubule-associated protein
neuroplasticity
Green Fluorescent Proteins
Notch signaling pathway
Biology
Transfection
Cellular and Molecular Neuroscience
Neuroblastoma
Norepinephrine
Serrate-Jagged Proteins
Developmental Neuroscience
Tubulin
Neurites
Humans
Enzyme Inhibitors
Receptor
Notch1
Growth cone
Cell Line
Transformed
Neurons
Protein Synthesis Inhibitors
pre-synaptic varicositie
Analysis of Variance
protein synthesi
Gene Expression Profiling
Calcium-Binding Proteins
Membrane Proteins
Cell Differentiation
Microarray Analysis
Synapsins
gene profile
Actins
Cell biology
Notch proteins
Immunoglobulin J Recombination Signal Sequence-Binding Protein
Dactinomycin
Jagged-1 Protein
Intercellular Signaling Peptides and Proteins
Microtubule-Associated Proteins
Signal Transduction
Zdroj: Developmental neurobiology. 69(6)
ISSN: 1932-8451
Popis: Notch proteins are definitely recognized as key regulators of the neuronal fate during embryo development, but their function in the adult brain is still largely unknown. We have previously demonstrated that Notch pathway stimulation increases microtubules stability followed by the remodeling of neuronal morphology with neurite varicosities loss, thicker neuritis, and enlarged growth cones. Here we show that the neurite remodeling is a dynamic event, dependent on transcription and translation, and with functional implications. Exposure of differentiated human SH-SY5Y neuroblastoma cells to the Notch ligand Jagged1 induces varicosities loss all along the neurites, accompanied by the redistribution of presynaptic vesicles and the decrease in neurotransmitters release. As evaluated by time lapse digital imaging, dynamic changes in neurite morphology were rapidly reversible and dependent on the activation of the Notch signaling pathway. In fact, it was prevented by the inhibition of the proteolytic gamma-secretase enzyme or the transcription machinery, and was mimicked by the transfection of the intracellular domain of Notch. One hour after treatment with Jagged1, several genes were downregulated. Many of these genes encode proteins that are known to be involved in protein synthesis. These data suggest that in adult neurons, Notch pathway activates a transcriptional program that regulates the equilibrium between varicosities formation and varicosities loss in the neuronal presynaptic compartment involving the expression and redistribution of both structural and functional proteins.
Databáze: OpenAIRE
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