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  Differential roles of postsynaptic density-93 isoforms in regulating synaptic transmission.

Krüger, J. M., Favaro, P. D., Liu, M., Kitlinska, A., Huang, X. J., Raabe, M., et al. (2013). Differential roles of postsynaptic density-93 isoforms in regulating synaptic transmission. Journal of Neuroscience, 33(39), 15504-15517. doi:10.1523/JNEUROSCI.0019-12.2013.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0014-73CB-6 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0028-1CF2-D
Genre: Journal Article

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Krüger, J. M., Author
Favaro, P. D., Author
Liu, M., Author
Kitlinska, A., Author
Huang, X. J., Author
Raabe, M.1, Author              
Akad, D. S., Author
Liu, Y., Author
Urlaub, H.1, Author              
Dong, Y., Author
Xu, W., Author
Schlüter, O. M., Author
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1Research Group of Bioanalytical Mass Spectrometry, MPI for biophysical chemistry, Max Planck Society, ou_578613              

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 Abstract: In the postsynaptic density of glutamatergic synapses, the discs large (DLG)-membrane-associated guanylate kinase (MAGUK) family of scaffolding proteins coordinates a multiplicity of signaling pathways to maintain and regulate synaptic transmission. Postsynaptic density-93 (PSD-93) is the most variable paralog in this family; it exists in six different N-terminal isoforms. Probably because of the structural and functional variability of these isoforms, the synaptic role of PSD-93 remains controversial. To accurately characterize the synaptic role of PSD-93, we quantified the expression of all six isoforms in the mouse hippocampus and examined them individually in hippocampal synapses. Using molecular manipulations, including overexpression, gene knockdown, PSD-93 knock-out mice combined with biochemical assays, and slice electrophysiology both in rat and mice, we demonstrate that PSD-93 is required at different developmental synaptic states to maintain the strength of excitatory synaptic transmission. This strength is differentially regulated by the six isoforms of PSD-93, including regulations of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor-active and inactive synapses, and activity-dependent modulations. Collectively, these results demonstrate that alternative combinations of N-terminal PSD-93 isoforms and DLG-MAGUK paralogs can fine-tune signaling scaffolds to adjust synaptic needs to regulate synaptic transmission.

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Language(s): eng - English
 Dates: 2013-09-25
 Publication Status: Published in print
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 Rev. Method: Peer
 Identifiers: DOI: 10.1523/JNEUROSCI.0019-12.2013
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Title: Journal of Neuroscience
Source Genre: Journal
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Pages: - Volume / Issue: 33 (39) Sequence Number: - Start / End Page: 15504 - 15517 Identifier: -