NTAK/neuregulin-2 secreted by astrocytes promotes survival and neurite outgrowth of neurons via ErbB3
| Autor: | Chizuka Ide, Norihiko Nakano, Michio Asahi, Takatoshi Nakagawa, Kenji Kanekiyo |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Nervous system Receptor ErbB-4 Receptor ErbB-3 Neurite Cell Survival Morpholines Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Epidermal growth factor ErbB Neurites medicine Animals Nerve Growth Factors Phosphorylation ERBB4 Neurons Canertinib Chemistry Kinase General Neuroscience Molecular biology Cell biology 030104 developmental biology medicine.anatomical_structure Astrocytes Culture Media Conditioned Quinazolines 030217 neurology & neurosurgery |
| Zdroj: | Neuroscience Letters. 622:88-94 |
| ISSN: | 0304-3940 |
| DOI: | 10.1016/j.neulet.2016.04.050 |
| Popis: | NTAK (neural- and thymus-derived activator for ErbB kinases), also known as neuregulin-2 (NRG2), is a member of the epidermal growth factor (EGF) family, which binds directly to ErbB3 and ErbB4, and transactivates ErbB2. NTAK/NRG2 is structurally homologous to NRG1. The biological function of NTAK/NRG2 still remains unknown, especially in the nervous system, whereas NRG1 is known to be essential for nervous system function. In the present study, we examined the functions of NTAK/NRG2 secreted from astrocytes to neurons. NTAK/NRG2 was expressed in both neurons and astrocytes, as evidenced by immunohistochemical staining and RT-PCR methods. The conditioned medium (CM) from astrocytes promoted survival and neurite outgrowth of neurons. The CM stimulated phosphorylation of ErbB3 in neurons. When phosphorylation of ErbB3 was blocked by AZD8931, an ErbB3 inhibitor, neuronal survival and neurite outgrowth were reduced. Conversely, canertinib, an ErbB4 inhibitor, did not affect survival or neurite outgrowth of neurons. Survival and neurite outgrowth of neurons were lower in CM of NTAK/NRG2-knockdown astrocytes than in the CM of control astrocytes, whereas the CM of NRG1-knockdown astrocytes had little effect on survival and neurite outgrowth. The present study demonstrated that NTAK/NRG2 secreted from astrocytes bound to ErbB3 on neurons, and promoted neuronal survival and neurite extension in vitro. |
| Databáze: | OpenAIRE |
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