Neuregulin induces GABA(A) receptor subunit expression and neurite outgrowth in cerebellar granule cells

Neuregulin (NRG), a growth and differentiation factor that signals via erbB receptor tyrosine kinases, has been shown to have biological effects in bo th the CNS and the peripheral nervous system. We report here that erbB4 is expressed in mature cerebellar granule cells, where it appears to be concen trated at the granule cell postsynaptic terminals. We also show that one fo rm of NRG, Ig-NRG, plays a crucial role in aspects of cerebellar granule ce ll development in vitro. First, Ig-NRG treatment of granule cells in cultur e selectively induces the expression of the GABA(A) receptor beta 2 subunit . This increase in subunit expression is paralleled by an increase in funct ional GABA(A) receptors. In contrast to its effects on GABA(A) receptor sub unit expression, Ig-NRG does not upregulate NMDA receptor N2B and N2C subun it expression. Second, we demonstrate that Ig-NRG also enhances neurite out growth from cultured granule cells. Ig-NRG does not, however, act as a surv ival factor for the granule cells. We have compared the effect of Ig-NRG wi th the effects of brain-derived neurotrophic factor (BDNF), a neurotrophin that exerts specific effects on granule cells in culture, and found that BD NF does not mimic the effects of Ig-NRG on GABA(A) receptor subunit express ion. Our results show that Ig-NRG has specific effects on granule cell deve lopment and maturation and may regulate these processes in vivo.