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Nuclear Localization of the p75 Neurotrophin Receptor Intracellular Domain*
Christopher N. Parkhurst1,
Niccoló Zampieri1, , and
Moses V. Chao2
From the Molecular Neurobiology Program, Skirball Institute for Biomolecular Medicine, and
the Departments of Cell Biology, Physiology and Neuroscience, and Psychiatry, New York University School of Medicine, New York, New York 10016
Abstract:
The p75 neurotrophin receptor, a member of the tumor necrosisfactor superfamily of receptors, undergoes an -secretase-mediatedrelease of its extracellular domain, followed by a -secretase-mediatedintramembrane cleavage. Like amyloid precursor protein and Notch,-secretase cleavage of the p75 receptor releases an intracellulardomain (ICD). However, it has been experimentally challengingto determine the precise subcellular localization and functionalconsequences of the p75 ICD. Here, we utilized a nuclear translocationassay and biochemical fractionation approaches to follow thefate of the ICD. We found that the p75 ICD can translocate tothe nucleus to activate a green fluorescent protein reportergene. Furthermore, the p75 ICD was localized in nuclear fractions.Chromatin immunoprecipitation experiments indicated that nervegrowth factor induced the association of endogenous p75 withthe cyclin E1 promoter. Expression of the p75 ICD resulted inmodulation of gene expression from this locus. These resultssuggest that the p75 ICD generated by -secretase cleavage iscapable of modulating transcriptional events in the nucleus.
2 To whom correspondence should be addressed: Skirball Inst. for Biomolecular Medicine, New York University School of Medicine, 540 First Ave., New York, NY 10016. Tel.: 212-263-0761; Fax: 212-263-0723; E-mail: chao{at}saturn.med.nyu.edu.
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EDITORS' CHOICE
L. Bryan Ray (23 February 2010) Sci. Signal.3 (110), ec63.
[DOI: 10.1126/scisignal.3110ec63] |Abstract »
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2
-secretase-mediated release of its extracellular domain, followed by a 
-secretase-mediated intramembrane cleavage. Like amyloid precursor protein and Notch, 
