Neuregulin

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.

Neuregulin family members

The neuregulin family includes:

• Neuregulin 1 (NRG1), with numerous discovered isoforms stemming from alternative splicing:
  • Type I NRG1; alternative names: Heregulin, NEU differentiation factor (NDF), or acetylcholine receptor inducing activity (ARIA)
  • Type II NRG1; alternative name: Glial Growth Factor-2 (GGF2);
  • Type III NRG1; alternative name: Sensory and motor neuron-derived factor (SMDF);
  • Type IV NRG1;
  • Type V NRG1;
  • Type VI NRG1; Types IV-VI are proteins with 3 novel N-terminal domains identified in 2004.
• Neuregulin 2 (NRG2);
• Neuregulin 3 (NRG3);
• Neuregulin 4 (NRG4);

In mammals, neuregulin family members are the products of 4 genes NRG1, NRG2, NRG3 and NRG4 respectively.

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, localization, 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.