Sez6l2 regulates phosphorylation of ADD and neuritogenesis

Hiroaki Yaguchi, Ichiro Yabe, Hidehisa Takahashi, Masashi Watanabe, Taichi Nomura, Takahiro Kano, Masaki Matsumoto, Keiichi I. Nakayama, Masahiko Watanabe, Shigetsugu Hatakeyama

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Increasing evidence shows that immune-mediated mechanisms may contribute to the pathogenesis of central nervous system disorders including cerebellar ataxias, as indicated by the aberrant production of neuronal surface antibodies. We previously reported a patient with cerebellar ataxia associated with production of a new anti-neuronal antibody, anti-seizure-related 6 homolog like 2 (Sez6l2). Sez6l2 is a type 1 membrane protein that is highly expressed in the hippocampus and cerebellar cortex and mice lacking Sez6l2 protein family members develop ataxia. Here we used a proteomics-based approach to show that serum derived from this patient recognizes the extracellular domain of Sez6l2 and that Sez6l2 protein binds to both adducin (ADD) and glutamate receptor 1 (GluR1). Our results indicate that Sez6l2 is one of the auxiliary subunits of the AMPA receptor and acts as a scaffolding protein to link GluR1 to ADD. Furthermore, Sez6l2 overexpression upregulates ADD phosphorylation, whereas siRNA-mediated downregulation of Sez612 prevents ADD phosphorylation, suggesting that Sez6l2 modulates AMPA-ADD signal transduction.

Original languageEnglish
Pages (from-to)234-241
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume494
Issue number1-2
DOIs
Publication statusPublished - Dec 9 2017

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Yaguchi, H., Yabe, I., Takahashi, H., Watanabe, M., Nomura, T., Kano, T., Matsumoto, M., Nakayama, K. I., Watanabe, M., & Hatakeyama, S. (2017). Sez6l2 regulates phosphorylation of ADD and neuritogenesis. Biochemical and Biophysical Research Communications, 494(1-2), 234-241. https://doi.org/10.1016/j.bbrc.2017.10.047