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The Journal of Neuroscience, December 15, 1999, 19(24):10757-10766
Neuregulin Induces GABAA Receptor Subunit Expression and Neurite Outgrowth in Cerebellar Granule Cells
Heather I. Rieff1, Lori T. Raetzman3, Douglas W. Sapp4, Hermes H. Yeh4, Ruth E. Siegel2, and Gabriel Corfas1 1 Division of Neuroscience and Department of Neurology, Children's Hospital and Harvard Medical School, and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02115, 2 Department of Pharmacology, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106-4965, 3 Department of Neuroscience, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106-4975, and 4 Department of Pharmacology and Neurology, Program in Neuroscience, University of Connecticut Health Center, Farmington, Connecticut 06030
Neuregulin (NRG), a growth and differentiation factor that signals via erbB receptor tyrosine kinases, has been shown to have biological effects in both the CNS and the peripheral nervous system. We report here that erbB4 is expressed in mature cerebellar granule cells, where it appears to be concentrated at the granule cell postsynaptic terminals. We also show that one form of NRG, Ig-NRG, plays a crucial role in aspects of cerebellar granule cell development in vitro. First, Ig-NRG treatment of granule cells in culture selectively induces the expression of the GABAA receptor
2 subunit. This increase in subunit expression is paralleled by an increase in functional GABAA receptors. In contrast to its effects on GABAA receptor subunit expression, Ig-NRG does not upregulate NMDA receptor N2B and N2C subunit expression. Second, we demonstrate that Ig-NRG also enhances neurite outgrowth from cultured granule cells. Ig-NRG does not, however, act as a survival factor for the granule cells. We have compared the effect of Ig-NRG with the effects of brain-derived neurotrophic factor (BDNF), a neurotrophin that exerts specific effects on granule cells in culture, and found that BDNF does not mimic the effects of Ig-NRG on GABAA receptor subunit expression. Our results show that Ig-NRG has specific effects on granule cell development and maturation and may regulate these processes in vivo.
Key words: erbB receptors; neuregulin; cerebellum; neurite outgrowth; GABAA receptors; neuronal differentiation; cerebellar granule cells
Copyright © 1999 Society for Neuroscience 0270-6474/99/192410757-10$05.00/0
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