Neuregulins are a sub-family of EGF-like molecules that have been shown to play multiple essential roles in vertebrate embryogenesis including: cardiac development, Schwann cell and oligodendrocyte differentiation, some aspects of neuronal development, as well as the formation of neuromuscular synapses [, ]. Included in the family are heregulin; neu differentiation factor; acetylcholine receptor synthesis stimulator; glial growth factor; and sensory and motor-neuron derived factor []. Multiple family members are generated by alternate splicing or by use of several cell type-specific transcription initiation sites. In general, they bind to and activate the erbB family of receptor tyrosine kinases (erbB2 (HER2), erbB3 (HER3), and erbB4 (HER4)), functioning both as heterodimers and homodimers.The transmembrane forms of neuregulin 1 (NRG1) are present within synaptic vesicles, including those containing glutamate []. After exocytosis, NRG1 is in the presynaptic membrane, where the ectodomain of NRG1 may be cleaved off. The ectodomain then migrates across the synaptic cleft and binds to and activates a member of the EGF-receptor family on the postsynaptic membrane. This has been shown to increase the expression of certain glutamate-receptor subunits. NRG1 appears to signal for glutamate-receptor subunit expression, localisation, and /or phosphorylation facilitating subsequent glutamate transmission. The NRG1 gene has been identified as a potential gene determining susceptibility to schizophrenia by a combination of genetic linkage and association approaches [].
Neuregulins are a sub-family of EGF-like molecules that have been shown to play multiple essential roles in vertebrate embryogenesis including: cardiac development, Schwann cell and oligodendrocyte differentiation, some aspects of neuronal development, as well as the formation of neuromuscular synapses [, ]. Included in the family are heregulin; neu differentiation factor; acetylcholine receptor synthesis stimulator; glial growth factor; and sensory and motor-neuron derived factor []. Multiple family members are generated by alternate splicing or by use of several cell type-specific transcription initiation sites. In general, they bind to and activate the erbB family of receptor tyrosine kinases (erbB2 (HER2), erbB3 (HER3), and erbB4 (HER4)), functioning both as heterodimers and homodimers.The transmembrane forms of neuregulin 1 (NRG1) are present within synaptic vesicles, including those containing glutamate []. After exocytosis, NRG1 is in the presynaptic membrane, where the ectodomain of NRG1 may be cleaved off. The ectodomain then migrates across the synaptic cleft and binds to and activates a member of the EGF-receptor family on the postsynaptic membrane. This has been shown to increase the expression of certain glutamate-receptor subunits. NRG1 appears to signal for glutamate-receptor subunit expression, localisation, and /or phosphorylation facilitating subsequent glutamate transmission. The NRG1 gene has been identified as a potential gene determining susceptibility to schizophrenia by a combination of genetic linkage and association approaches []. Membrane-anchored Nrg-1 isoforms consist of a variable N-terminal extracellular domain and a conserved transmembrane and C-terminal cytoplasmic domains []. This entry represents the C-terminal, intracellular domain.
