BECN1/Beclin1 is recruited into lipid rafts by prion to activate autophagy in response to amyloid β 42

Jihoon Nah, Jong Ok Pyo, Sunmin Jung, Seung Min Yoo, Tae In Kam, Jae Woong Chang, Jonghee Han, Seong Soo A. An, Takashi Onodera, Yong Keun Jung

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Prion protein (PRNP) has been implicated in various types of neurodegenerative diseases. Although much is known about prion diseases, the function of cellular PRNP remains cryptic. Here, we show that PRNP mediates amyloid β1-42 (Aβ42)-induced autophagy activation through its interaction with BECN1. Treatment with Aβ42 enhanced autophagy flux in neuronal cells. Aβ42-induced autophagy activation, however, was impaired in prnp-knockout primary cortical neurons and Prnp-knockdown or prnp-knockout neuronal cells. Immunoprecipitation assays revealed that PRNP interacted with BECN1 via the BCL2-binding domain of BECN1. This interaction promoted the subcellular localization of BECN1 into lipid rafts of the plasma membrane and enhanced activity of PtdIns3K (whose catalytic subunit is termed PIK3C3, mammalian ortholog of yeast VPS34) in lipid rafts by generating PtdIns3P in response to Aβ42. Further, the levels of lipid rafts that colocalized with BECN1, decreased in the brains of aged C57BL/6 mice, as did PRNP. These results suggested that PRNP interacts with BECN1 to recruit the PIK3C3 complex into lipid rafts and thus activates autophagy in response to Aβ42, defining a novel role of PRNP in the regulation of autophagy.

Original languageEnglish (US)
Pages (from-to)2009-2021
Number of pages13
JournalAutophagy
Volume9
Issue number12
DOIs
StatePublished - Dec 1 2013

Keywords

  • Amyloid beta
  • Autophagy
  • BECN1
  • Lipid rafts
  • Prion protein

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    Nah, J., Pyo, J. O., Jung, S., Yoo, S. M., Kam, T. I., Chang, J. W., Han, J., An, S. S. A., Onodera, T., & Jung, Y. K. (2013). BECN1/Beclin1 is recruited into lipid rafts by prion to activate autophagy in response to amyloid β 42. Autophagy, 9(12), 2009-2021. https://doi.org/10.4161/auto.26118