PMID- 10594059 OWN - NLM STAT- MEDLINE DCOM- 20000106 LR - 20240421 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 19 IP - 24 DP - 1999 Dec 15 TI - Neuregulin induces GABA(A) receptor subunit expression and neurite outgrowth in cerebellar granule cells. PG - 10757-66 AB - 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 GABA(A) receptor beta2 subunit. This increase in subunit expression is paralleled by an increase in functional GABA(A) receptors. In contrast to its effects on GABA(A) 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 GABA(A) 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. FAU - Rieff, H I AU - Rieff HI AD - Division of Neuroscience, Department of Neurology, Children's Hospital and Harvard Medical School, Harvard Medical School, Boston, Massachusetts 02115, USA. FAU - Raetzman, L T AU - Raetzman LT FAU - Sapp, D W AU - Sapp DW FAU - Yeh, H H AU - Yeh HH FAU - Siegel, R E AU - Siegel RE FAU - Corfas, G AU - Corfas G LA - eng GR - R01 NS35884/NS/NINDS NIH HHS/United States GR - R01 NS035884/NS/NINDS NIH HHS/United States GR - P30 HD018655/HD/NICHD NIH HHS/United States GR - 632EY07110-05/EY/NEI NIH HHS/United States GR - T32 EY007110/EY/NEI NIH HHS/United States GR - R01 NS034317/NS/NINDS NIH HHS/United States GR - P30-HD18655/HD/NICHD NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Neuregulins) RN - 0 (Protein Isoforms) RN - 0 (Receptors, GABA-A) RN - EC 2.7.10.1 (ErbB Receptors) RN - EC 2.7.10.1 (Erbb4 protein, rat) RN - EC 2.7.10.1 (Receptor, ErbB-4) SB - IM MH - Aging/metabolism MH - Animals MH - Animals, Newborn/growth & development MH - Cell Survival/physiology MH - Cells, Cultured MH - Cerebellum/cytology/metabolism/*physiology MH - ErbB Receptors/metabolism MH - Neuregulins/*pharmacology MH - Neurites/*drug effects/*physiology MH - Neurons/drug effects/metabolism/*physiology MH - Protein Isoforms/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Receptor, ErbB-4 MH - Receptors, GABA-A/drug effects/*metabolism MH - Synapses/metabolism MH - Up-Regulation PMC - PMC6784934 EDAT- 1999/12/14 00:00 MHDA- 1999/12/14 00:01 PMCR- 2000/06/15 CRDT- 1999/12/14 00:00 PHST- 1999/12/14 00:00 [pubmed] PHST- 1999/12/14 00:01 [medline] PHST- 1999/12/14 00:00 [entrez] PHST- 2000/06/15 00:00 [pmc-release] AID - 3721 [pii] AID - 10.1523/JNEUROSCI.19-24-10757.1999 [doi] PST - ppublish SO - J Neurosci. 1999 Dec 15;19(24):10757-66. doi: 10.1523/JNEUROSCI.19-24-10757.1999.