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Regulation of gephyrin assembly and glycine receptor synaptic stability
- Source :
- The Journal of biological chemistry. 281(40)
- Publication Year :
- 2006
-
Abstract
- Gephyrin is required for the formation of clusters of the glycine receptor (GlyR) in the neuronal postsynaptic membrane. It can make trimers and dimers through its N- and C-terminal G and E domains, respectively. Gephyrin oligomerization could thus create a submembrane lattice providing GlyR-binding sites. We investigated the relationships between the stability of cell surface GlyR and the ability of gephyrin splice variants to form oligomers. Using truncated and full-length gephyrins we found that the 13-amino acid sequence (cassette 5) prevents G domain trimerization. Moreover, E domain dimerization is inhibited by the gephyrin central L domain. All of the gephyrin variants bind GlyR beta subunit cytoplasmic loop with high affinity regardless of their cassette composition. Coexpression experiments in COS-7 cells demonstrated that GlyR bound to gephyrin harboring cassette 5 cannot be stabilized at the cell surface. This gephyrin variant was found to deplete synapses from both GlyR and gephyrin in transfected neurons. These data suggest that the relative expression level of cellular variants influence the overall oligomerization pattern of gephyrin and thus the turnover of synaptic GlyR.
- Subjects :
- Cell
Biochemistry
Rats, Sprague-Dawley
Receptors, Glycine
Chlorocebus aethiops
medicine
Animals
splice
Molecular Biology
Glycine receptor
Cells, Cultured
Neurons
Gephyrin
biology
Membrane Proteins
Cell Biology
Transfection
Rats
Postsynaptic membrane
medicine.anatomical_structure
Cytoplasm
G-domain
COS Cells
Synapses
biology.protein
Biophysics
Carrier Proteins
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 281
- Issue :
- 40
- Database :
- OpenAIRE
- Journal :
- The Journal of biological chemistry
- Accession number :
- edsair.doi.dedup.....18b439f6c6899535d4139f3003327d86