NRG1

Neuregulin 1 is important for synaptic plasticity, inhibiting the amygdala (to shut down anxiety), myelination (Schwann cell maturation, survival, and motility), heart function (cardiac growth factor) and tumor suppression…

Direct ligand for ERBB3 and ERBB4 tyrosine kinase receptors. Concomitantly recruits ERBB1 and ERBB2 coreceptors, resulting in ligand-stimulated tyrosine phosphorylation and activation of the ERBB receptors. The multiple isoforms perform diverse functions such as inducing growth and differentiation of epithelial, glial, neuronal, and skeletal muscle cells; inducing expression of acetylcholine receptor in synaptic vesicles during the formation of the neuromuscular junction; stimulating lobuloalveolar budding and milk production in the mammary gland and inducing differentiation of mammary tumor cells; stimulating Schwann cell proliferation; implication in the development of the myocardium such as trabeculation of the developing heart. Isoform 10 may play a role in motor and sensory neuron development. Binds to ERBB4 (PubMed:10867024, PubMed:7902537). Binds to ERBB3 (PubMed:20682778). Acts as a ligand for integrins and binds (via EGF domain) to integrins ITGAV:ITGB3 or ITGA6:ITGB4. Its binding to integrins and subsequent ternary complex formation with integrins and ERRB3 are essential for NRG1-ERBB signaling. Induces the phosphorylation and activation of MAPK3/ERK1, MAPK1/ERK2 and AKT1 (PubMed:20682778). Ligand-dependent ERBB4 endocytosis is essential for the NRG1-mediated activation of these kinases in neurons.

• Neuregulin 1 is important for synaptic plasticity, GABAergic function within the amygdala (to shut down anxiety), myelination (Schwann cell maturation, survival, and motility), heart function (cardiac growth factor), tumor suppression
• Neuregulin 1  increases  axonal 7 nAChR.
• Neuregulin 1 is decreased in schizophrenia.
• Neuregulin 1 decreases IL-1², IL-6, IL-10, IL-8, IL12-p70, and TNF-.

More detailed information:

• Neuregulin 1 (NRG1)

• Associated with

  • Schizophrenia [R]

  • Bipolar disorder [R]

  • Alzheimer’s disease (AD) [R]

  • Anxiety-like behaviors [R]

  • Heart development and maintenance problems [R]

    • Chronic heart failure and heart abnormality

  • Many fast growing tumors [R]

Advanced information:

• Migration of neuronal receptors in cerebral cortex [R]

• pi3K/Akt activates NRG1 ability to prevent release of Aβ1-42 -induced LDH release [R]

• pi3K/Akt activates NRG1 prevents accumulation of oxygen reactive species in the primary cortical neurons [R]

• NRG1 interacts with Receptor Tyrosine-protein Kinase erbB-3 (ERBB3) [R]

  • ErbB3 functions as an epidermal growth factor receptor [R]

• NRG1 interacts with LIM domain kinase 1 (LIMK1) [R]

  • LIMK1 works as an intracellular signaling pathway [R]

  • NRG1 to treat Alzheimer’s disease (AD) [R]

Use of recombinant human NRG1 (rhNRG-1) as a drug for treatment of chronic heart failure [R]

     Covered on Genetics Home Reference: Hirschsprung diseaseFrom NCBI Gene: Schizophrenia 6From UniProt: A chromosomal aberration involving NRG1 produces gamma-heregulin. Translocation t(8;11) with TENM4. The translocation fuses the 5'-end of TENM4 to NRG1 (isoform 8). The product of this translocation was first thought to be an alternatively spliced isoform. Gamma-heregulin is a soluble activating ligand for the ERBB2-ERBB3 receptor complex and acts as an autocrine growth factor in a specific breast cancer cell line (MDA-MB-175). Not detected in breast carcinoma samples, including ductal, lobular, medullary, and mucinous histological types, neither in other breast cancer cell lines.

     From NCBI Gene: The protein encoded by this gene is a membrane glycoprotein that mediates cell-cell signaling and plays a critical role in the growth and development of multiple organ systems. An extraordinary variety of different isoforms are produced from this gene through alternative promoter usage and splicing. These isoforms are expressed in a tissue-specific manner and differ significantly in their structure, and are classified as types I, II, III, IV, V and VI. Dysregulation of this gene has been linked to diseases such as cancer, schizophrenia, and bipolar disorder (BPD). [provided by RefSeq, Apr 2016] From UniProt: Direct ligand for ERBB3 and ERBB4 tyrosine kinase receptors. Concomitantly recruits ERBB1 and ERBB2 coreceptors, resulting in ligand-stimulated tyrosine phosphorylation and activation of the ERBB receptors. The multiple isoforms perform diverse functions such as inducing growth and differentiation of epithelial, glial, neuronal, and skeletal muscle cells; inducing expression of acetylcholine receptor in synaptic vesicles during the formation of the neuromuscular junction; stimulating lobuloalveolar budding and milk production in the mammary gland and inducing differentiation of mammary tumor cells; stimulating Schwann cell proliferation; implication in the development of the myocardium such as trabeculation of the developing heart. Isoform 10 may play a role in motor and sensory neuron development. Binds to ERBB4 (PubMed:10867024, PubMed:7902537). Binds to ERBB3 (PubMed:20682778). Acts as a ligand for integrins and binds (via EGF domain) to integrins ITGAV:ITGB3 or ITGA6:ITGB4. Its binding to integrins and subsequent ternary complex formation with integrins and ERRB3 are essential for NRG1-ERBB signaling. Induces the phosphorylation and activation of MAPK3/ERK1, MAPK1/ERK2 and AKT1 (PubMed:20682778). Ligand-dependent ERBB4 endocytosis is essential for the NRG1-mediated activation of these kinases in neurons.

Nicotine, Alpha GPC/Acetylcholine