Sez6l2 regulates phosphorylation of ADD and neuritogenesis

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

Research output: Contribution to journalArticle

2 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

Fingerprint

Phosphorylation
Seizures
Glutamate Receptors
Cerebellar Ataxia
Signal transduction
Proteins
AMPA Receptors
Neurology
Small Interfering RNA
Anti-Idiotypic Antibodies
Membrane Proteins
Cerebellar Cortex
adducin
Central Nervous System Diseases
Ataxia
Proteomics
Antibodies
Signal Transduction
Hippocampus
Up-Regulation

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Yaguchi, H., Yabe, I., Takahashi, H., Watanabe, M., Nomura, T., Kano, T., ... 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

Sez6l2 regulates phosphorylation of ADD and neuritogenesis. / Yaguchi, Hiroaki; Yabe, Ichiro; Takahashi, Hidehisa; Watanabe, Masashi; Nomura, Taichi; Kano, Takahiro; Matsumoto, Masaki; Nakayama, Keiichi; Watanabe, Masahiko; Hatakeyama, Shigetsugu.

In: Biochemical and Biophysical Research Communications, Vol. 494, No. 1-2, 09.12.2017, p. 234-241.

Research output: Contribution to journalArticle

Yaguchi, H, Yabe, I, Takahashi, H, Watanabe, M, Nomura, T, Kano, T, Matsumoto, M, Nakayama, K, Watanabe, M & Hatakeyama, S 2017, 'Sez6l2 regulates phosphorylation of ADD and neuritogenesis', Biochemical and Biophysical Research Communications, vol. 494, no. 1-2, pp. 234-241. https://doi.org/10.1016/j.bbrc.2017.10.047
Yaguchi H, Yabe I, Takahashi H, Watanabe M, Nomura T, Kano T et al. Sez6l2 regulates phosphorylation of ADD and neuritogenesis. Biochemical and Biophysical Research Communications. 2017 Dec 9;494(1-2):234-241. https://doi.org/10.1016/j.bbrc.2017.10.047
Yaguchi, Hiroaki ; Yabe, Ichiro ; Takahashi, Hidehisa ; Watanabe, Masashi ; Nomura, Taichi ; Kano, Takahiro ; Matsumoto, Masaki ; Nakayama, Keiichi ; Watanabe, Masahiko ; Hatakeyama, Shigetsugu. / Sez6l2 regulates phosphorylation of ADD and neuritogenesis. In: Biochemical and Biophysical Research Communications. 2017 ; Vol. 494, No. 1-2. pp. 234-241.
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