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Postsynaptic density-93 interacts with the delta2 glutamate receptor subunit at parallel fiber synapses
K W Roche1, C D Ly, R S Petralia
1Laboratory of Neurochemistry, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892, USA. rochek@nidcd.nih.gov
Summary
Glutamate receptor delta2 interacts with PSD-93 in the cerebellum. This interaction influences delta2 receptor clustering at parallel fiber synapses, but PSD-93 alone doesn't dictate delta2 localization.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- The glutamate receptor subunit delta2 (δ2R) exhibits developmental regulation in the cerebellum.
- δ2R is found at parallel fiber (PF) and climbing fiber (CF) synapses early in development, but restricted to PF synapses in adults.
Purpose of the Study:
- To identify proteins interacting with the C terminus of δ2R.
- To investigate the role of interacting proteins in δ2R trafficking and synaptic localization.
Main Methods:
- Yeast two-hybrid screening using the cytosolic C terminus of δ2R.
- Coexpression in heterologous cells to assess clustering.
- Ultrastructural localization studies.
Main Results:
- PSD-93, a member of the PSD-95 family, specifically binds to δ2R.
- PSD-93 clusters δ2R in heterologous cells; mutations disrupting binding also disrupt clustering.
- Ultrastructural analysis reveals colocalization of PSD-93 and δ2R at PF synapses.
Conclusions:
- PSD-93 interacts with and clusters the glutamate receptor subunit δ2.
- While PSD-93 is present at both PF and CF synapses in adult rats, δ2R is only at PF synapses.
- PSD-93 presence alone is insufficient to determine δ2R synaptic expression, suggesting other regulatory factors are involved.