About NRG1 / Neuregulin:
Neuregulin is a type of protein which researchers believe plays a vital role in the development of the nervous system across a wide variety of species. The protein, also sometimes called “glial growth factor,” is required by organisms in the development of vertebrate eggs, the heart, Schwann cell differentiation, and neuronal development.
NRG1 Interactions
Neuregulin interacts with ErbB receptors, a subfamily of tyrosine kinase proteins found on the surface of cells. Neuregulin, therefore, is a cell signalling protein which instructs cells to perform specific actions. In humans, neuregulin interacts directly with the four ErbB receptors called Erb1, Erb2 (Neu or HER2), ErbB3 (HER3) and Erb4 (HER4). These receptors are slightly different from each other, but all rely on the ligand-binding N-terminal domain - a specific site which neuregulin can bind to the cell and deliver instructions.
Of course, the docking site for neuregulin is also used by a variety of other molecules and is involved in the regulation of intracellular signalling cascades, primarily through the stimulation of the mitogen-activated protein kinase pathway.
Neuregulin Mechanisms
Neuregulins exert their effect through the process of autophosphorylation of tyrosine residues in the part of the cell which contains the cytoplasm. The phosphorylated areas provide neuregulin with a “docking site” - a place where it can chemically interact with the cell and deliver the intended message. Most of the cell signalling happens through the stimulation of the Rar mitogen-activated protein kinase pathway, the PI3K pathway and the PLC-gamma/PKC pathway.
Another potential signalling mechanism for the ErbB4 receptors is presenilin-dependant intramembrane proteolysis by gamma-secretase - a process that releases the C-terminal fragment, which signals to the nucleus of the target cells to regulate gene expression.
NRG-1 Function
In humans, neuregulin has a variety of functions. It is a trophic factor which contains an epidermal growth factor: a chemical which signals to the body to create new cell growth in the dermal layer. It’s also been found to be important in neutral development thanks to the role it plays in axon guidance, oligodendrocyte development and the formation of synapses - the gaps between nerve cells which convey chemical information related to brain cell activity.
Neuregulin may also play a role in the development of mental conditions like schizophrenia. Neuregulin is a risk gene which was first identified from a large multigenerational Icelandic pedigree. The because neuregulin affects glutamatergic, nicotinic and GABAergic transmission, it may affect human brain organisation. There’s a debate right now as to whether NERG1 and ErbB proteins are altered in schizophrenia tissue, especially in at-risk brain regions, like the hippocampus. So far, the evidence is mixed. Post-mortem studies show that there is relatively little change in neuregulin or ErbB levels in schizophrenic tissue. However, these tissues display greater neuregulin-induced activation of ErbB receptors.
NRG 1 Structure
Neuregulin, or NRG1, is a group of protein ligands that act on the epidermal growth factor receptor family. There are currently six isoforms of neuregulin presently known to science, some of which may play a role in the pathology of schizophrenia, though how exactly this happens remains unclear.