PLoS ONE (Jan 2013)

Hsc70 is a novel interactor of NF-kappaB p65 in living hippocampal neurons.

  • Christin Klenke,
  • Darius Widera,
  • Thomas Engelen,
  • Janine Müller,
  • Thomas Noll,
  • Karsten Niehaus,
  • M Lienhard Schmitz,
  • Barbara Kaltschmidt,
  • Christian Kaltschmidt

DOI
https://doi.org/10.1371/journal.pone.0065280
Journal volume & issue
Vol. 8, no. 6
p. e65280

Abstract

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Signaling via NF-κB in neurons depends on complex formation with interactors such as dynein/dynactin motor complex and can be triggered by synaptic activation. However, so far a detailed interaction map for the neuronal NF-κB is missing. In this study we used mass spectrometry to identify novel interactors of NF-κB p65 within the brain. Hsc70 was identified as a novel neuronal interactor of NF-κB p65. In HEK293 cells, a direct physical interaction was shown by co-immunoprecipitation and verified via in situ proximity ligation in healthy rat neurons. Pharmacological blockade of Hsc70 by deoxyspergualin (DSG) strongly decreased nuclear translocation of NF-κB p65 and transcriptional activity shown by reporter gene assays in neurons after stimulation with glutamate. In addition, knock down of Hsc70 via siRNA significantly reduced neuronal NF-κB activity. Taken together these data provide evidence for Hsc70 as a novel neuronal interactor of NF-κB p65.