Implication of c-secretase in neuregulin-induced maturation of oligodendrocytes

Increasing evidences suggest that, after neuregulin (NRG) stimulation, ErbB4 undergoes a series of proteolysis, including c-secretase cleavage. The released ErbB4 intracellular domain (EICD) is translocated into nucleus and has a transcriptional function. Although NRG–ErbB4 signaling mediates maturation of oligodendrocytes (OLs), the role of EICD and c-secretase in this process remains elusive. Here, we showed that NRG–ErbB4 interaction accumulated EICD in the nucleus and promoted the expression of myelin basic protein expression in OLs. Conversely, inhibitor of ErbB4 or c-secretase blocked the capacity of NRG. Nuclear accumulation of EICD did not influence maturation of neurons and astrocytes and early development of OLs. We also found that EICD translocation accorded a temporal pattern, consistent with the developmental gradient of hippocampus. Our data suggest that c-secretase activation and EICD nuclear translocation are required for OL maturation induced by NRG, and ErbB4 acts as a functional receptor depending on a new signaling cascade. 2003 Elsevier Inc. All rights reserved.