Implication of gamma-secretase in neuregulin-induced maturation of oligodendrocytes.
Increasing evidences suggest that, after neuregulin (NRG) stimulation, ErbB4 undergoes a series of proteolysis, including gamma-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 gamma-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 gamma-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 gamma-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.
Lai
Chen
C
Institute of Neuroscience, Shanghai Institutes for Biological Science, Chinese Academy of Science, 200031 Shanghai, PR China.
Feng
Linyin
L
D021581:Active Transport, Cell Nucleus; D053829:Amyloid Precursor Protein Secretases; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D010450:Endopeptidases / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D066246:ErbB Receptors / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000737:chemistry; D008856:Microscopy, Fluorescence; D009186:Myelin Sheath / Q000737:chemistry / Q000378:metabolism; D020880:Neuregulins / Q000737:chemistry*; D009836:Oligodendroglia / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D051381:Rats; D017207:Rats, Sprague-Dawley; D066247:Receptor, ErbB-4; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors; D014158:Transcription, Genetic
D008565:Membrane Proteins; D020880:Neuregulins; C086745:periaxin; D066246:ErbB Receptors; C587691:Erbb4 protein, rat; D066247:Receptor, ErbB-4; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases