2. Academic Validation
  3. Regulation of neuronal survival and morphology by the E3 ubiquitin ligase RNF157

Regulation of neuronal survival and morphology by the E3 ubiquitin ligase RNF157

  • Cell Death Differ. 2015 Apr;22(4):626-42. doi: 10.1038/cdd.2014.163.
A Matz 1,  S-J Lee 1,  N Schwedhelm-Domeyer 1,  D Zanini 2,  A Holubowska 3,  M Kannan 1,  M Farnworth 1,  O Jahn 4,  M C Göpfert 2,  J Stegmüller 3
Affiliations

Affiliations

  • 1 Cellular and Molecular Neurobiology Group, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
  • 2 Department of Cellular Neurobiology, Schwann-Schleiden Center, Julia Lermontowa Weg 3, University of Göttingen, Göttingen, Germany.
  • 3 1] Cellular and Molecular Neurobiology Group, Max Planck Institute of Experimental Medicine, Göttingen, Germany [2] Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Göttingen, Germany.
  • 4 1] Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Göttingen, Germany [2] Proteomics Group, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
PMID: 25342469 DOI: 10.1038/cdd.2014.163
Abstract

Neuronal health is essential for the long-term integrity of the brain. In this study, we characterized the novel E3 ubiquitin ligase ring finger protein 157 (RNF157), which displays a brain-dominant expression in mouse. RNF157 is a homolog of the E3 ligase mahogunin ring finger-1, which has been previously implicated in spongiform neurodegeneration. We identified RNF157 as a regulator of survival in cultured neurons and established that the ligase activity of RNF157 is crucial for this process. We also uncovered that independently of its ligase activity, RNF157 regulates dendrite growth and maintenance. We further identified the adaptor protein APBB1 (amyloid beta precursor protein-binding, family B, member 1 or Fe65) as an interactor and proteolytic substrate of RNF157 in the control of neuronal survival. Here, the nuclear localization of Fe65 together with its interaction partner RNA-binding protein SART3 (squamous cell carcinoma antigen recognized by T cells 3 or Tip110) is crucial to trigger Apoptosis. In summary, we described that the E3 ligase RNF157 regulates important aspects of neuronal development.

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