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.
Murphy
Sean P
SP
Institute of Cell Signalling, University of Nottingham, Nottingham, UK. seanm6@u.washington.edu
Bielby-Clarke
Keren
K
D000818:Animals; D000831:Animals, Newborn; D002531:Cerebellum / Q000166:cytology; D000076122:Disks Large Homolog 4 Protein; D066246:ErbB Receptors / Q000378:metabolism*; D051528:Guanylate Kinases; D047468:Immunoprecipitation / Q000379:methods; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D020890:Neuregulin-1 / Q000378:metabolism* / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D017434:Protein Structure, Tertiary; D066247:Receptor, ErbB-4; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D020890:Neuregulin-1; D066246:ErbB Receptors; C587690:Erbb4 protein, mouse; D066247:Receptor, ErbB-4; D051528:Guanylate Kinases