Neuregulin signaling in neurons depends on ErbB4 interaction with PSD-95

Neuregulin-1 signaling molecules have various roles in the nervous system, including effects on neuronal migration and differentiation. In mouse cerebellar granule neurons the effects of neuregulin-1 (type I) are mediated by a homo-dimeric ErbB4 receptor, which can interact with the PSD-95 protein through a C-terminal motif. To determine whether this interaction is critical for signaling we introduced into granule cells a decoy peptide representing the C-terminal 20 amino acids of the mouse ErbB4 receptor. Exposure of unloaded cells to neuregulin-1 did not alter neurite density but increased average neurite length by 50%. In contrast, granule cell cultures loaded with the decoy peptide were unresponsive to the ligand. We conclude that the association of ErbB4 with PSD-95 is important for neuregulin-induced neuronal differentiation.