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Gene Review

Nrg1  -  neuregulin 1

Rattus norvegicus

Synonyms: Ndf, Pro-NRG1, Pro-neuregulin-1, membrane-bound isoform
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Disease relevance of Nrg1

  • NRG-1 reduced ischemia/reperfusion injury, indicating that it may act as an endogenous neuroprotective factor against stroke [1].
  • Here, we report our findings that rats pre-treated with NRG-1 protein, undergoing cerebral ischemia 30 min later, had increased motor performance and less cerebral infarction than untreated rats [1].
  • We examined the expression of NRG-1 and its receptors, the erbB membrane tyrosine kinases, in JS1 cells, a rapidly proliferating line derived from a chemically induced rat malignant peripheral nerve sheath tumor (MPNST) [2].
  • These results suggest that NRG1 may contribute to the reduction in GABAergic synaptic activity in hippocampal CA1 pyramidal neurons that normally occurs during early postnatal development, and that alterations in NRG1 signaling in the hippocampus may contribute to schizophrenia and epilepsy [3].
  • Neuregulin localized immunocytochemically was present on neurites of cultured dorsal root ganglion neurons, and it was released into the medium in a form that promoted receptor tyrosine phosphorylation [4].

High impact information on Nrg1


Biological context of Nrg1


Anatomical context of Nrg1

  • Neuregulin signaling on glucose transport in muscle cells [12].
  • In this study, we examined the signaling pathway required for a recombinant active neuregulin-1 isoform (rhHeregulin-beta(1), 177-244, HRG) to stimulate glucose uptake in L6E9 myotubes [12].
  • beta-Neuregulin and autocrine mediated survival of Schwann cells requires activity of Ets family transcription factors [14].
  • High levels of an NRG-like activity are also present in some human peripheral nerve sheath tumors, suggesting that NRG-1 isoforms may be involved in the development of these neoplasms [2].
  • In the present report, we show that, in the hippocampus, NRG1 is expressed in a pattern suggesting that it regulates synapse development in the CA1 region [3].

Associations of Nrg1 with chemical compounds

  • These effects of NRG1 occur without concomitant changes in glutamate receptors and other synaptic proteins [3].
  • However, in contrast to what has been shown in other synapses, NRG1 reduces the expression of gamma-aminobutyric acid (GABA)A receptors alpha subunits in hippocampal slices, and the mean amplitude of GABAergic miniature inhibitory postsynaptic currents (IPSCs) in hippocampal CA1 pyramidal neurons, without affecting IPSC kinetics or frequency [3].
  • Relative to nontransformed Schwann cells, JS1 cells overexpress the NRG-1 receptor erbB3 and its erbB2 coreceptor; JS1 erbB2 transcripts show no evidence of the activating mutation commonly found in N-ethyl-N-nitrosourea-induced neoplasms [2].
  • In O2A progenitor cells and oligodendrocytes, recombinant neuregulin induces the rapid tyrosine phosphorylation of only HER4 [4].
  • Identification of a neuregulin and protein-tyrosine phosphatase response element in the nicotinic acetylcholine receptor epsilon subunit gene: regulatory role of an Rts transcription factor [15].

Physical interactions of Nrg1


Regulatory relationships of Nrg1


Other interactions of Nrg1


Analytical, diagnostic and therapeutic context of Nrg1


  1. Neuregulin-1 reduces ischemia-induced brain damage in rats. Shyu, W.C., Lin, S.Z., Chiang, M.F., Yang, H.I., Thajeb, P., Li, H. Neurobiol. Aging (2004) [Pubmed]
  2. Constitutive activation of the neuregulin-1/ErbB receptor signaling pathway is essential for the proliferation of a neoplastic Schwann cell line. Frohnert, P.W., Stonecypher, M.S., Carroll, S.L. Glia (2003) [Pubmed]
  3. Neuregulin1 downregulates postsynaptic GABAA receptors at the hippocampal inhibitory synapse. Okada, M., Corfas, G. Hippocampus. (2004) [Pubmed]
  4. Axonal neuregulin signals cells of the oligodendrocyte lineage through activation of HER4 and Schwann cells through HER2 and HER3. Vartanian, T., Goodearl, A., Viehöver, A., Fischbach, G. J. Cell Biol. (1997) [Pubmed]
  5. Alternative neural crest cell fates are instructively promoted by TGFbeta superfamily members. Shah, N.M., Groves, A.K., Anderson, D.J. Cell (1996) [Pubmed]
  6. Cdk5 is involved in neuregulin-induced AChR expression at the neuromuscular junction. Fu, A.K., Fu, W.Y., Cheung, J., Tsim, K.W., Ip, F.C., Wang, J.H., Ip, N.Y. Nat. Neurosci. (2001) [Pubmed]
  7. Evidence that axon-derived neuregulin promotes oligodendrocyte survival in the developing rat optic nerve. Fernandez, P.A., Tang, D.G., Cheng, L., Prochiantz, A., Mudge, A.W., Raff, M.C. Neuron (2000) [Pubmed]
  8. GGF/neuregulin is a neuronal signal that promotes the proliferation and survival and inhibits the differentiation of oligodendrocyte progenitors. Canoll, P.D., Musacchio, J.M., Hardy, R., Reynolds, R., Marchionni, M.A., Salzer, J.L. Neuron (1996) [Pubmed]
  9. Glial growth factor/neuregulin inhibits Schwann cell myelination and induces demyelination. Zanazzi, G., Einheber, S., Westreich, R., Hannocks, M.J., Bedell-Hogan, D., Marchionni, M.A., Salzer, J.L. J. Cell Biol. (2001) [Pubmed]
  10. Activity-dependent regulation of Neu differentiation factor/neuregulin expression in rat brain. Eilam, R., Pinkas-Kramarski, R., Ratzkin, B.J., Segal, M., Yarden, Y. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  11. Neu differentiation factor stimulates phosphorylation and activation of the Sp1 transcription factor. Alroy, I., Soussan, L., Seger, R., Yarden, Y. Mol. Cell. Biol. (1999) [Pubmed]
  12. Neuregulin signaling on glucose transport in muscle cells. Cantó, C., Suárez, E., Lizcano, J.M., Griñó, E., Shepherd, P.R., Fryer, L.G., Carling, D., Bertran, J., Palacín, M., Zorzano, A., Gumà, A. J. Biol. Chem. (2004) [Pubmed]
  13. Release of the neuregulin functional polypeptide requires its cytoplasmic tail. Liu, X., Hwang, H., Cao, L., Wen, D., Liu, N., Graham, R.M., Zhou, M. J. Biol. Chem. (1998) [Pubmed]
  14. beta-Neuregulin and autocrine mediated survival of Schwann cells requires activity of Ets family transcription factors. Parkinson, D.B., Langner, K., Namini, S.S., Jessen, K.R., Mirsky, R. Mol. Cell. Neurosci. (2002) [Pubmed]
  15. Identification of a neuregulin and protein-tyrosine phosphatase response element in the nicotinic acetylcholine receptor epsilon subunit gene: regulatory role of an Rts transcription factor. Sapru, M.K., Florance, S.K., Kirk, C., Goldman, D. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  16. The neuron-glia signal beta neuregulin induces sustained CREB phosphorylation on Ser-133 in cultured rat Schwann cells. Tabernero, A., Stewart, H.J., Jessen, K.R., Mirsky, R. Mol. Cell. Neurosci. (1998) [Pubmed]
  17. Neuregulin stimulates myogenic differentiation in an autocrine manner. Kim, D., Chi, S., Lee, K.H., Rhee, S., Kwon, Y.K., Chung, C.H., Kwon, H., Kang, M.S. J. Biol. Chem. (1999) [Pubmed]
  18. Regulation of NMDA receptors by neuregulin signaling in prefrontal cortex. Gu, Z., Jiang, Q., Fu, A.K., Ip, N.Y., Yan, Z. J. Neurosci. (2005) [Pubmed]
  19. Induction of Cdk5 activity in rat skeletal muscle after nerve injury. Fu, W.Y., Fu, A.K., Lok, K.C., Ip, F.C., Ip, N.Y. Neuroreport (2002) [Pubmed]
  20. Reciprocal signaling between spiral ganglion neurons and Schwann cells involves neuregulin and neurotrophins. Hansen, M.R., Vijapurkar, U., Koland, J.G., Green, S.H. Hear. Res. (2001) [Pubmed]
  21. Expression of alpha2a-2b neuregulin-1 is associated with early peripheral nerve repair along muscle-enriched tubes. Nicolino, S., Raimondo, S., Tos, P., Battiston, B., Fornaro, M., Geuna, S., Perroteau, I. Neuroreport (2003) [Pubmed]
  22. A real-time quantitative PCR comparative study between rat optic and sciatic nerves: determination of neuregulin-1 mRNA levels. Martínez, J.C., Malavé, C., Bosch, I., Castillo, C., Núñez, J., Villegas, G.M., Villegas, R. Brain Res. Mol. Brain Res. (2004) [Pubmed]
  23. Neuregulin receptors, erbB3 and erbB4, are localized at neuromuscular synapses. Zhu, X., Lai, C., Thomas, S., Burden, S.J. EMBO J. (1995) [Pubmed]
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