Neuregulins (also known as @entity6048 , @entity6536 , heregulin, @entity6536 ) are a family of widely expressed growth and differentiation factors. Neuregulins secreted from motor neurons accumulate at maturing neuromuscular junctions, where they stimulate transcription of genes encoding specific @entity934 receptors. How these factors function at central synapses, however, is unknown. In the maturing cerebellum, neuregulins are concentrated in glutamatergic mossy fibres that innervate granule cells in the internal granule-cell layer. We have analysed the effects of neuregulins on the expression of genes encoding @entity143 ( @entity1024 ) receptors in the cerebellum, because receptor composition changes dramatically as expression of the receptor @entity21413 subunit is specifically induced in neurons in the internal granule-cell layer during synaptogenesis. Here we report that addition of a neuregulin-beta isoform to cultured cerebellar slices specifically increases the expression of @entity21413 messenger RNAs by at least 100-fold; effects are only minor with a neuregulin-alpha isoform. This stimulation of @entity21413 expression requires synaptic activity by @entity143 receptors, as well as neuregulin-beta. Addition of the @entity143 -receptor-channel blocker AP-5 prevents upregulation of the @entity21413 subunit by neuregulin, whereas an @entity140 /kainate-receptor antagonist does not. Consistent with these effects of neuregulin, we find that granule cells express its receptors @entity1722 and @entity12251 before the @entity21413 subunit of the @entity143 receptor. Our results indicate that neuregulins regulate the composition of neurotransmitter receptors in maturing synapses in the brain, in a manner analogous to the neuromuscular junction.

Neuregulin-beta induces expression of an XXXX -receptor subunit.

@entity1024 :: ('CHEBI:31882', 'Chemical') :: ['N-methyl-D-aspartate'] @entity1722 :: ('2064', 'Gene') :: ['ErbB2'] @entity12251 :: ('2066', 'Gene') :: ['ErbB4'] @entity21413 :: ('2905', 'Gene') :: ['NR2C'] @entity143 :: ('CHEBI:6121', 'Chemical') :: ['NMDA'] @entity140 :: ('MESH:D018350', 'Chemical') :: ['AMPA'] @entity6536 :: ('3084', 'Gene') :: ['NDF', 'GGF'] @entity6048 :: ('641700', 'Gene') :: ['ARIA'] @entity934 :: ('MESH:D000109', 'Chemical') :: ['acetylcholine']
@entity143 :: (CHEBI:6121,Chemical) :: ['NMDA']
