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Description

Neuregulin-1 (UniProt: Q02297, also known as Acetylcholine receptor-inducing activity, ARIA, Breast cancer cell differentiation factor p45, Glial growth factor, Heregulin, HRG, Neu differentiation factor, Sensory and motor neuron-derived factor) is encoded by the NRG1 (also known as GGF, HGL, HRGA, NDF, SMDF) gene (Gene ID: 3084) in human. Neuregulin-1 is a single-pass type 1 membrane protein that acts as a direct ligand for ErbBB3 and ErbB4 tyrosine kinase receptors. It concomitantly recruits ERBB1 and ERBB2 coreceptors, resulting in ligand-stimulated tyrosine phosphorylation and activation of the ERBB receptors. Eleven isoforms of Neuregulin-1 are known that are produced by alternative splicing. They have been classified as type I (isoforms with an Ig domain and a glycosylation domain) type II NRGs (isoforms with an Ig domain, but no glycosylation domain). These multiple isoforms perform diverse cellular functions, such as inducing growth and differentiation of epithelial, glial, neuronal, and skeletal muscle cells and inducing expression of acetylcholine receptor in synaptic vesicles during the formation of the neuromuscular junction. Proteolytic cleavage close to the plasma membrane on the external face leads to the release of the soluble growth factor form. Dual cleavage of Neuregulin-1 by beta-secretase 1 (BACE1) and ADAM17 is shown to liberate EGF-like domain, which stimulates ErbB3 signaling. (Ref.: Fleck, D., et a. (2013). J. Neurosci. 33(18):7856-7869).