Brain-derived neurotrophic factor (BDNF) promotes molecular polarization and differentiation of immature neuroblastoma cells into definitive neurons
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
32389647
DOI
10.1016/j.bbamcr.2020.118737
PII: S0167-4889(20)30095-1
Knihovny.cz E-zdroje
- Klíčová slova
- Microtubule-associated protein, Neuronal differentiation, Proximity ligation assay, SH-SY5Y neuroblastoma, Synaptic markers, Tau protein,
- MeSH
- biologické markery MeSH
- buněčná diferenciace genetika MeSH
- lidé MeSH
- mozkový neurotrofický faktor genetika metabolismus MeSH
- nádorové buněčné linie MeSH
- neuroblastom genetika metabolismus patologie MeSH
- neurogeneze genetika MeSH
- neurony cytologie metabolismus MeSH
- reaktivní formy kyslíku MeSH
- signální transdukce MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- biologické markery MeSH
- mozkový neurotrofický faktor MeSH
- reaktivní formy kyslíku MeSH
Throughout development, neuronal progenitors undergo complex transformation into polarized nerve cells, warranting the directional flow of information in the neural grid. The majority of neuronal polarization studies have been carried out on rodent-derived precursor cells, programmed to develop into neurons. Unlike rodent neuronal cells, SH-SY5Y cells derived from human bone marrow present a sub-clone of neuroblastoma line, with their transformation into neuron-like cells showing a range of highly instructive neurobiological characteristics. We applied two-step retinoic acid (RA) and brain-derived neurotrophic factor (BDNF) protocol to monitor the conversion of undifferentiated SH-SY5Y into neuron-like cells with distinctly polarized axon-dendritic morphology and formation of bona fide synaptic connections. We show that BDNF is a key driver and regulator of the expression of axonal marker tau and dendritic microtubule-associated protein-2 (MAP2), with their sorting to distinct cellular compartments. Using selective kinase inhibitors downregulating BDNF-TrkB signaling, we demonstrate that constitutive activation of TrkB receptor is essential for the maintenance of established polarization morphology. Importantly, the proximity ligation assay applied in our preparation demonstrates that differentiating neuron-like cells develop elaborate synaptic connections enriched with hallmark pre- and postsynaptic proteins. Described herein findings highlight several fundamental processes related to neuronal polarization and synaptogenesis in human-derived cells, which are of major relevance to neurobiology and translational neuroscience.
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