BACE1 regulates the proliferation and cellular functions of Schwann cells

Xiangyou Hu, Hailong Hou, Chinthasagar Bastian, Wanxia He, Shupeng Qiu, Yingying Ge, Xinhua Yin, Grahame J. Kidd, Sylvain Brunet, Bruce D. Trapp, Selva Baltan, Riqiang Yan

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

BACE1 is an indispensable enzyme for generating β-amyloid peptides, which are excessively accumulated in brains of Alzheimer's patients. However, BACE1 is also required for proper myelination of peripheral nerves, as BACE1-null mice display hypomyelination. To determine the precise effects of BACE1 on myelination, here we have uncovered a role of BACE1 in the control of Schwann cell proliferation during development. We demonstrate that BACE1 regulates the cleavage of Jagged-1 and Delta-1, two membrane-bound ligands of Notch. BACE1 deficiency induces elevated Jag-Notch signaling activity, which in turn facilitates proliferation of Schwann cells. This increase in proliferation leads to shortened internodes and decreased Schmidt–Lanterman incisures. Functionally, evoked compound action potentials in BACE1-null nerves were significantly smaller and slower, with a clear decrease in excitability. BACE1-null nerves failed to effectively use lactate as an alternative energy source under conditions of increased physiological activity. Correlatively, BACE1-null mice showed reduced performance on rotarod tests. Collectively, our data suggest that BACE1 deficiency enhances proliferation of Schwann cell due to the elevated Jag1/Delta1-Notch signaling, but fails to myelinate axons efficiently due to impaired the neuregulin1-ErbB signaling, which has been documented.

Original languageEnglish (US)
Pages (from-to)712-726
Number of pages15
JournalGLIA
Volume65
Issue number5
DOIs
StatePublished - May 1 2017
Externally publishedYes

Keywords

  • Alzheimer's β-secretase
  • BACE1
  • Jagged
  • myelin sheath
  • myelination
  • node of Ranvier
  • Notch
  • Schmidt–Lanterman clefts

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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