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Synapse-Associated Protein-97 Isoform-Specific Regulation of Surface AMPA Receptors and Synaptic Function in Cultured Neurons
Abstract
Members of the synapse-associated protein-97 (SAP97) family of scaffold proteins have been implicated as central organizers of synaptic junctions to build macromolecular signaling complexes around specific postsynaptic neurotransmitter receptors. In this regard, SAP97 has been suggested to regulate the synaptic localization of glutamate receptor type 1 subunits of the AMPA-type glutamate receptors. To test this hypothesis directly, we assessed the effects of SAP97 overexpression on surface expression of synaptic AMPA receptors. We find that recombinant SAP97 not only becomes concentrated at synaptic junctions but also leads to an increase in synaptic AMPA receptors, spine enlargement, and an increase in miniature EPSC (mEPSC) frequency, indicating that SAP97 has both postsynaptic and presynaptic effects on synaptic transmission. Synaptic targeting of SAP97, increased surface AMPA receptors, and increased mEPSC frequency are dependent on the presence of specific alternatively spliced sequences in SAP97 that encode a protein 4.1 binding site. These results suggest that SAP97 can affect the synaptic recruitment of AMPA receptors and spine morphology and that these effects may be regulated by alternative splicing.
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“The expression of AMPA receptors in spines is dependent on F-actin11,17 and scaffolding proteins18,19.”
From Structural basis of long-term potentiation in single dendritic spines (2004) · cites this paper as [19]
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“In addition, spines from mature neurons are often larger, and a recent study describes the correlation between spine size and AMPA responses (Matsuzaki et al., 2001).”
BackgroundPSD-95 Involvement in Maturation of Excitatory Synapses
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Stargazin regulates synaptic targeting of AMPA receptors by two distinct mechanisms
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Central sensitization: a generator of pain hypersensitivity by central neural plasticity
Latremoliere, A., & Woolf, C. J. (2009) · The Journal of Pain · doi:10.1016/j.jpain.2009.06.012 · Cited by 3,913
Structural basis of long-term potentiation in single dendritic spines
Matsuzaki, M., Honkura, N., Ellis-Davies, G. C. R., & Kasai, H. (2004) · Nature · doi:10.1038/nature02617 · Cited by 2,483
Hippocampal GABAergic Inhibitory Interneurons
Pelkey, K. A., Chittajallu, R., Craig, M. T., Tricoire, L., Wester, J. C., & McBain, C. J. (2017) · Physiological Reviews · doi:10.1152/physrev.00007.2017 · Cited by 889
Arc/Arg3.1 interacts with the endocytic machinery to regulate AMPA receptor trafficking
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Self-citationArc/Arg3.1 Mediates Homeostatic Synaptic Scaling of AMPA Receptors
Shepherd, J. D., Rumbaugh, G., Wu, J., Chowdhury, S., Plath, N., Kuhl, D., Huganir, R. L., & Worley, P. F. (2006) · Neuron · doi:10.1016/j.neuron.2006.08.034 · Cited by 779
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Metadata
- Authors
- Rumbaugh, G., Sia, G.-M., Garner, C. C., & Huganir, R. L.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2003-06-01
- Volume
- 23
- Issue
- 11
- Pages
- 4567-4576
- ISSN
- 0270-6474
- 1529-2401
- Cited by
- 152
- References
- 5
- Language
- en
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