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

Autor: Peer-Hendrik Kuhn, Manfred Wuhrer, Gerhard Rammes, Marc Aurel Busche, Hung-En Hsia, Rohit Kumar, Jana Hartmann, Birgit Blank, Mai Ly Tran, Jenny M. Gunnersen, Pan Gao, Gökhan Güner, Johanna Tüshaus, Julia von Blume, Martina Pigoni, Stephan A. Müller, Bulat Ramazanov, Merav D. Shmueli, Stefan F. Lichtenthaler, Agnes L. Hipgrave Ederveen, Thomas Koeglsperger, Jasenka Rudan Njavro, Christophe Mulle
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Nervous system
Glycosylation
Kainate receptor
chemistry.chemical_compound
Mice
0302 clinical medicine
Receptors
Kainic Acid
Membrane & Intracellular Transport
Receptor
genetics [Nerve Tissue Proteins]
genetics [Receptors
Kainic Acid]
Mice
Knockout
0303 health sciences
General Neuroscience
Pyramidal Cells
BACE1
Articles
Transport protein
Cell biology
metabolism [Pyramidal Cells]
Protein Transport
medicine.anatomical_structure
Ectodomain
protein trafficking
Kainic acid
HNK-1
Nerve Tissue Proteins
Biology
General Biochemistry
Genetics and Molecular Biology
metabolism [Receptors
Kainic Acid]
Article
SEZ6
03 medical and health sciences
ddc:570
medicine
Animals
GluK2/3
Molecular Biology
CA1 Region
Hippocampal
Secretory pathway
030304 developmental biology
metabolism [CA1 Region
Hippocampal]
metabolism [Nerve Tissue Proteins]
General Immunology and Microbiology
GluK2
HNK‐1
chemistry
030217 neurology & neurosurgery
Neuroscience
Zdroj: EMBO JOURNAL
The EMBO Journal
The EMBO journal 39(15), e103457 (2020). doi:10.15252/embj.2019103457
EMBO Journal, 39(15). WILEY
DOI: 10.15252/embj.2019103457
Popis: 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.
The beta‐secretase/BACE1 substrate SEZ6 regulates the trafficking of GluK2/3 to modulate their subcellular localization and glycosylation.
Databáze: OpenAIRE
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