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Seizure protein 6 controls glycosylation and trafficking of kainate receptor subunits GluK2 and GluK3
Author(s) -
Pigoni Martina,
Hsia HungEn,
Hartmann Jana,
Rudan Njavro Jasenka,
Shmueli Merav D,
Müller Stephan A,
Güner Gökhan,
Tüshaus Johanna,
Kuhn PeerHendrik,
Kumar Rohit,
Gao Pan,
Tran Mai Ly,
Ramazanov Bulat,
Blank Birgit,
Hipgrave Ederveen Agnes L,
Von Blume Julia,
Mulle Christophe,
Gunnersen Jenny M,
Wuhrer Manfred,
Rammes Gerhard,
Busche Marc Aurel,
Koeglsperger Thomas,
Lichtenthaler Stefan F
Publication year - 2020
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2019103457
Subject(s) - kainate receptor , biology , microbiology and biotechnology , ampa receptor , kainic acid , neuroscience , ectodomain , receptor , glutamate receptor , biochemistry
Seizure protein 6 (SEZ6) is required for the development and maintenance of the nervous system, is a major substrate of the protease BACE1 and is linked to Alzheimer's disease (AD) and psychiatric disorders, but its molecular functions are not well understood. Here, we demonstrate that SEZ6 controls glycosylation and cell surface localization of kainate receptors composed of GluK2/3 subunits. Loss of SEZ6 reduced surface levels of GluK2/3 in primary neurons and reduced kainate‐evoked currents in CA1 pyramidal neurons in acute hippocampal slices. Mechanistically, loss of SEZ6 in vitro and in vivo prevented modification of GluK2/3 with the human natural killer‐1 (HNK‐1) glycan, a modulator of GluK2/3 function. SEZ6 interacted with GluK2 through its ectodomain and promoted post‐endoplasmic reticulum transport of GluK2 in the secretory pathway in heterologous cells and primary neurons. Taken together, SEZ6 acts as a new trafficking factor for GluK2/3. This novel function may help to better understand the role of SEZ6 in neurologic and psychiatric diseases.