Synaptic SAP97 Isoforms Regulate AMPA Receptor Dynamics and Access to Presynaptic Glutamate
Abstract
The synaptic insertion of GluR1-containing AMPA-type glutamate receptors (AMPARs) is critical for synaptic plasticity. However, mechanisms responsible for GluR1 insertion and retention at the synapse are unclear. The synapse-associated protein SAP97 directly binds GluR1 and participates in its forward trafficking from the Golgi network to the plasma membrane. Whether SAP97 also plays a role in scaffolding GluR1 at the postsynaptic membrane is controversial, attributable to its expression as a collection of alternatively spliced isoforms with ill-defined spatial and temporal distributions. In the present study, we have used live imaging and electrophysiology to demonstrate that two postsynaptic, N-terminal isoforms of SAP97 directly modulate the levels, dynamics, and function of synaptic GluR1-containing AMPARs. Specifically, the unique N-terminal domains confer distinct subsynaptic localizations onto SAP97, targeting the palmitoylated α-isoform to the postsynaptic density (PSD) and the L27 domain-containing β-isoform primarily to non-PSD, perisynaptic regions. Consequently, α- and βSAP97 differentially influence the subsynaptic localization and dynamics of AMPARs by creating binding sites for GluR1-containing receptors within their respective subdomains. These results indicate that N-terminal splicing of SAP97 can control synaptic strength by regulating the distribution of AMPARs and, hence, their responsiveness to presynaptically released glutamate.
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The effects of SAP97 overexpression on synaptic transmission are influenced by isoforms of SAP97, compensation with other PSD-MAGUKs, or matureness of synapse.
“The effects of SAP97 overexpression on synaptic transmission seem to be influenced by many factors, such as isoforms of SAP97 (Schlu ¨ter et al., 2006;Waites et al., 2009), compensation with other PSD-MAGUKs (Schlu ¨ter et al., 2006;Howard et al., 2010), or matureness of synapse (Howard et al., 2010).”
From The Brain-Enriched MicroRNA miR-9-3p Regulates Synaptic Plasticity and Memory (2016) · cites this paper as Waites et al., 2009
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Cites
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- Authors
- Waites, C. L., Specht, C. G., Härtel, K., Leal-Ortiz, S., Genoux, D., Li, D., Drisdel, R. C., Jeyifous, O., Cheyne, J. E., Green, W. N., Montgomery, J. M., & Garner, C. C.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2009-04-08
- Volume
- 29
- Issue
- 14
- Pages
- 4332-4345
- ISSN
- 0270-6474
- 1529-2401
- PMC
- PMC3230533
- Cited by
- 97
- References
- 4
- Language
- en
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