Notch signaling inhibits PC12 cell neurite outgrowth via RBP-J-dependent and -independent mechanisms.
The Notch signaling pathway has been implicated in the control of neurite extension, although the mechanisms are unknown. In this report, we studied the role of RBP-J/CBF-1 activation, the primary mediator of Notch signaling, in Notch-mediated regulation of neurite outgrowth in PC12 cells. Expression of constitutively active Notch proteins decreased neurite length and number after NGF treatment. In contrast, an inactive Notch protein had no effect on neurite extension. A dominant negative RBP-J construct prevented the reduction of neurite outgrowth by Notch. Conversely, an activated form of RBP-J decreased neurite length but failed to reduce neurite number. In summary, Notch activation inhibited PC12 cell neurite outgrowth by both RBP-J-dependent and -independent pathways.
Levy
Oren A
OA
Department of Neurology, Emory University School of Medicine, Atlanta, Ga 30322, USA. alevey@emory.edu
Lah
James J
JJ
Levey
Allan I
AI
D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism; D048429:Cell Size; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005799:Genes, Dominant; D017930:Genes, Reporter; D006801:Humans; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D020932:Nerve Growth Factor / Q000494:pharmacology; D016501:Neurites / Q000648:ultrastructure*; D009687:Nuclear Proteins; D016716:PC12 Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D017434:Protein Structure, Tertiary; D051381:Rats; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins / Q000502:physiology; D017384:Sequence Deletion; D014157:Transcription Factors; D014162:Transfection
D004268:DNA-Binding Proteins; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D008565:Membrane Proteins; C497761:NOTCH1 protein, human; C497762:Notch1 protein, mouse; C497763:Notch1 protein, rat; D009687:Nuclear Proteins; C497570:RBPJ protein, human; C497571:Rbpj protein, mouse; C497572:Rbpjl2 protein, rat; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D020932:Nerve Growth Factor