Neuregulin1/ErbB4-induced migration in ST14A striatal progenitors: calcium-dependent mechanisms and modulation by NMDA receptor activation

BMC Neuroscience

Research Article

Silvia Farcito¹  Giovanna Gambarotta¹  Federica Fregnan¹  Valentina Licheri¹  Pollyanna Zamburlin¹  Giulia Pregno²  Isabelle Perroteau³  Davide Lovisolo³  Patrizia Bovolin³ 

[1] Department of Animal & Human Biology, University of Turin, Via Accademia Albertina 13, Turin, Italy;Department of Animal & Human Biology, University of Turin, Via Accademia Albertina 13, Turin, Italy;Department of Anatomy, Pharmacology and Forensic Medicine and National Institute of Neuroscience-Torino, Corso Massimo D'Azeglio 52, Turin, Italy;Department of Animal & Human Biology, University of Turin, Via Accademia Albertina 13, Turin, Italy;Neuroscience Institute of Turin (NIT), Interdepartmental Centre of Advanced Studies in Neuroscience, University of Turin, Italy;

关键词: Neuronal Migration;    Transwell Assay;    ErbB4 Receptor;    NR3B Subunit;    NMDAR Subunit;   

DOI  :  10.1186/1471-2202-12-103

 received in 2011-03-30, accepted in 2011-10-12,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundA number of studies have separately shown that the neuregulin1 (NRG1)/ErbB4 system and NMDA-type glutamate receptors (NMDARs) are involved in several aspects of neuronal migration. In addition, intracellular calcium fluctuations play central roles in neuronal motility. Stable expression of the tyrosine kinase receptor ErbB4 promotes migratory activity in the neural progenitor cell line ST14A upon NRG1 stimulation. In this work we analyzed the potential interactions between the NRG1/ErbB4 system and NMDARs in the ST14A migratory process as well as its calcium dependence.ResultsRT-PCR studies have shown that both native ST14A cells (non-expressing ErbB4), as well as ErbB4-transfected cells express low levels of a restricted number of NMDAR subunits: NR1, NR2C, NR2D and NR3B. The resulting NMDAR would form Ca2+ channels characterized by low Mg2+-sensitivity and low Ca2+-permeability, generating small, long-lasting currents. Ca2+-imaging experiments showed slow [Ca2+]i increases in 45% of the cells following 8 μM NMDA stimulation. Basal migration of ErbB4-transfected ST14A cells was unaffected by 18 hrs NMDA incubation. However, over the same incubation time, NMDA was able to significantly enhance NRG1-induced migration. Pre-incubation with the intracellular calcium chelator BAPTA-AM reduced both NRG1- and NRG1/NMDA-stimulated migration, suggesting the involvement of Ca2+ in these processes. NRG1 stimulation of ErbB4-transfected ST14A cells induced a sustained, long-lasting increase in [Ca2+]i, in 99% of the cells. These intracellular Ca2+ signals could be ascribed to both release from intracellular stores and influx from the extracellular medium trough a mechanism of store-operated calcium entry (SOCE). Short-time co-incubation of NMDA and NRG1 did not substantially modify the NRG1-induced intracellular calcium signals.ConclusionsIn summary, NRG1 stimulation of the ErbB4 receptor exerts a sustained [Ca2+]i increase in ST14A neural progenitors; NRG1-induced migration is Ca2+-dependent and can be positively modulated by activation of the NMDA receptor.

【 授权许可】

Unknown   
© Pregno et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.