Anti-Sez6l2 antibody detected in a patient with immune-mediated cerebellar ataxia inhibits complex formation of GluR1 and Sez6l2
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Autoantibodies are important for some cerebellar ataxias [2, 4]. We previously detected a new anti-neuronal antibody, anti-seizure-related 6 homolog like 2 (Sez6l2) antibody, in a cerebellar ataxia patient . Sez6l2 is highly expressed in the hippocampus and cerebellar cortex and is one of the type 1 membrane proteins [3, 5]. We previously showed that Sez6l2 protein binds to both adducin (ADD) and glutamate receptor 1 (GluR1) and that Sez6l2 may be a modulator of AMPA receptor function via the regulation of ADD phosphorylation . Our previous 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 . GluR1 is an important protein constructing the AMPA receptor, which is one of the target receptors for autoimmune-mediated neurological diseases . Furthermore, we previously showed that Sez6l2 and GluR1 directly bind using their extracellular domains and that the patient’s serum...
We are grateful to Prof. Hidenao Sasaki for helpful comments. We thank Shoko Shimizu for preparation of this manuscript. This work was supported by JSPS KAKENHI Grant number 25893006.
HY, IY and HT designed and performed experiments, analyzed and interpreted data and drafted the manuscript and figures. MW, TN, TK, MW and SH conceived and designed the study and critically revised the manuscript. All authors have seen and agree with the content of the manuscript. HY and IY contributed equally to this work.
Compliance with ethical standards
Conflicts of interest
All authors state that there is no conflict of interest.
This study was approved by the Institutional Review Board of Hokkaido University Hospital.
Written informed consent was obtained from the patient (Protocol number 012-0167).
- 1.Hoftberger R, van Sonderen A, Leypoldt F, Houghton D, Geschwind M, Gelfand J, Paredes M, Sabater L, Saiz A, Titulaer MJ, Graus F, Dalmau J (2015) Encephalitis and AMPA receptor antibodies: novel findings in a case series of 22 patients. Neurology 84:2403–2412CrossRefPubMedPubMedCentralGoogle Scholar
- 4.Mitoma H, Adhikari K, Aeschlimann D, Chattopadhyay P, Hadjivassiliou M, Hampe CS, Honnorat J, Joubert B, Kakei S, Lee J, Manto M, Matsunaga A, Mizusawa H, Nanri K, Shanmugarajah P, Yoneda M, Yuki N (2016) Consensus paper: neuroimmune mechanisms of cerebellar ataxias. Cerebellum (London, England) 15:213–232CrossRefGoogle Scholar
- 5.Miyazaki T, Hashimoto K, Uda A, Sakagami H, Nakamura Y, Saito SY, Nishi M, Kume H, Tohgo A, Kaneko I, Kondo H, Fukunaga K, Kano M, Watanabe M, Takeshima H (2006) Disturbance of cerebellar synaptic maturation in mutant mice lacking BSRPs, a novel brain-specific receptor-like protein family. FEBS Lett 580:4057–4064CrossRefPubMedGoogle Scholar