Acute inactivation of PSD-95 destabilizes AMPA receptors at hippocampal synapses.
Enviado por Guillermo Yudowski el
Título | Acute inactivation of PSD-95 destabilizes AMPA receptors at hippocampal synapses. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Autores | Yudowski, GA, Olsen, O, Adesnik, H, Marek, KW, Bredt, DS |
Journal | PLoS One |
Volume | 8 |
Issue | 1 |
Pagination | e53965 |
Date Published | 2013 |
ISSN | 1932-6203 |
Palabras clave | Animals, Cercopithecus aethiops, COS Cells, Hippocampus, Humans, Intracellular Signaling Peptides and Proteins, Kv1.4 Potassium Channel, Light, Membrane Proteins, Molecular Imaging, Neurons, Protein Stability, Protein Transport, Pyramidal Cells, Rats, Receptors, AMPA, Synapses |
Abstract | Postsynatptic density protein (PSD-95) is a 95 kDa scaffolding protein that assembles signaling complexes at synapses. Over-expression of PSD-95 in primary hippocampal neurons selectively increases synaptic localization of AMPA receptors; however, mice lacking PSD-95 display grossly normal glutamatergic transmission in hippocampus. To further study the scaffolding role of PSD-95 at excitatory synapses, we generated a recombinant PSD-95-4c containing a tetracysteine motif, which specifically binds a fluorescein derivative and allows for acute and permanent inactivation of PSD-95. Interestingly, acute inactivation of PSD-95 in rat hippocampal cultures rapidly reduced surface AMPA receptor immunostaining, but did not affected NMDA or transferrin receptor localization. Acute photoinactivation of PSD-95 in dissociated neurons causes ∼80% decrease in GluR2 surface staining observed by live-cell microscopy within 15 minutes of PSD-95-4c ablation. These results confirm that PSD-95 stabilizes AMPA receptors at postsynaptic sites and provides insight into the dynamic interplay between PSD-95 and AMPA receptors in live neurons. |
DOI | 10.1371/journal.pone.0053965 |
Alternate Journal | PLoS ONE |
PubMed ID | 23342049 |
PubMed Central ID | PMC3546964 |
Grant List | 1P30NS069258 / NS / NINDS NIH HHS / United States DA023444 / DA / NIDA NIH HHS / United States R00 DA023444 / DA / NIDA NIH HHS / United States |