Notch Activation Induces Neurite Remodeling and Functional Modifications in SH-SY5Y Neuronal Cells

被引:19
作者
Ferrari-Toninelli, Giulia [1 ,2 ]
Bonini, Sara Anna [1 ,2 ]
Uberti, Daniela [1 ,2 ]
Napolitano, Francesco [3 ]
Stante, Maria [3 ]
Santoro, Federica [3 ]
Minopoli, Giuseppina [3 ]
Zambrano, Nicola [3 ]
Russo, Tommaso [3 ]
Memo, Maurizio [1 ,2 ]
机构
[1] Univ Brescia, Dept Biomed Sci & Biotechnol, Brescia, Italy
[2] Univ Brescia, Natl Inst Neurosci Italy, Brescia, Italy
[3] Univ Naples Federico II, CEINGE Biotecnol Avanzate, Dipartimento Biochim & Biotecnol Med, Naples, Italy
关键词
neuroplasticity; pre-synaptic varicosities; gene profile; protein synthesis; NA release; HUMAN NEUROBLASTOMA SH-SY5Y; NEUROTROPHIC FACTOR; PROTEIN-SYNTHESIS; MESSENGER-RNA; HIPPOCAMPAL-NEURONS; RIBOSOMAL-PROTEIN; RETINOIC ACID; LINE SH-SY5Y; BRAIN; EXPRESSION;
D O I
10.1002/dneu.20710
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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. (C) 2009 Wiley Periodicals, Inc. Develop Neurobiol 69: 378-391, 2009
引用
收藏
页码:378 / 391
页数:14
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