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  Seizure protein 6 controls glycosylation and trafficking of kainate receptor subunits GluK2 and GluK3

Pigoni, M., Hsia, H.-E., Hartmann, J., Rudan Njavro, J., Shmueli, M. D., Mueller, S. A., et al. (2020). Seizure protein 6 controls glycosylation and trafficking of kainate receptor subunits GluK2 and GluK3. EMBO JOURNAL, e103457. doi:10.15252/embj.2019103457.

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 Creators:
Pigoni, Martina1, Author
Hsia, Hung-En1, Author
Hartmann, Jana1, Author
Rudan Njavro, Jasenka1, Author
Shmueli, Merav D.1, Author
Mueller, Stephan A.1, Author
Guener, Goekhan1, Author
Tueshaus, Johanna1, Author
Kuhn, Peer-Hendrik1, Author
Kumar, Rohit1, Author
Gao, Pan1, Author
Tran, Mai Ly2, Author           
Ramazanov, Bulat1, Author
Blank, Birgit1, Author
Hipgrave Ederveen, Agnes L.1, Author
von Blume, Julia2, Author           
Mulle, Christophe1, Author
Gunnersen, Jenny M.1, Author
Wuhrer, Manfred1, Author
Rammes, Gerhard1, Author
Busche, Marc Aurel1, AuthorKoeglsperger, Thomas1, AuthorLichtenthaler, Stefan F.1, Author more..
Affiliations:
1external, ou_persistent22              
2von Blume, Julia / Molecular Basis of Protein Trafficking, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565173              

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Free keywords: AUXILIARY SUBUNIT; LOCALIZED EXPRESSION; ALZHEIMERS-DISEASE; CARBOHYDRATE; BACE1; BRAIN; SEZ-6; PHOSPHORYLATION; PREVALENCE; EXTRACTIONBACE1; GluK2; 3; HNK-1; protein trafficking; SEZ6;
 Abstract: 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 SEZ6in vitroandin vivoprevented 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.

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Language(s): eng - English
 Dates: 2020
 Publication Status: Published online
 Pages: 24
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000541543900001
DOI: 10.15252/embj.2019103457
 Degree: -

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Title: EMBO JOURNAL
Source Genre: Journal
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Publ. Info: 111 RIVER ST, HOBOKEN 07030-5774, NJ USA : WILEY
Pages: - Volume / Issue: - Sequence Number: e103457 Start / End Page: - Identifier: ISSN: 0261-4189