Quaternary Structure, Protein Dynamics, and Synaptic Function of SAP97 Controlled by L27 Domain Interactions

Nakagawa, Terunaga; Futai, Kensuke; Lashuel, Hilal A.; Lo, Irene M.C.; Okamoto, Kenichi; Walz, Thomas; Hayashi, Yasunori; Sheng, Morgan

doi:10.1016/j.neuron.2004.10.012

Cited by 234 publications

(315 citation statements)

References 63 publications

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“…However, we found that the exchange of PSD-95-GFP was slow at the PSD (Fig. S4 B-D), consistent with previous work (22,25,26,31). Preincubation of neurons with jasplakinolide or latrunculin for 15 min did not affect the low rate or extent of PSD-95-GFP fluorescence recovery (Fig.…”

Section: Resultssupporting

confidence: 92%

“…5. It will be important to assess whether these or other oligomeric interactions of PSD proteins (22,39,40) confer stability to the complex as a whole or to subsets of proteins.…”

Section: Discussionmentioning

confidence: 99%

“…Recent live-imaging experiments have focused on the accumulation and dispersal of PSD scaffolds during synaptogenesis or synapse loss (19)(20)(21)(22), the translocation of assembled PSD scaffolds in developing neurons as synapses form (23), or the rates of exchange of various PSD constituents (22,(24)(25)(26). However, the submicron size of the PSD has hindered analysis of its morphology and internal architecture in living neurons.…”

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confidence: 99%

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Structural plasticity with preserved topology in the postsynaptic protein network

Blanpied

Kerr

Ehlers

2008

Proc. Natl. Acad. Sci. U.S.A.

119

104

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The size, shape, and molecular arrangement of the postsynaptic density (PSD) determine the function of excitatory synapses in the brain. Here, we directly measured the internal dynamics of scaffold proteins within single living PSDs, focusing on the principal scaffold protein PSD-95. We found that individual PSDs undergo rapid, continuous changes in morphology driven by the actin cytoskeleton and regulated by synaptic activity. This structural plasticity is accompanied by rapid fluctuations in internal scaffold density over submicron distances. Using targeted photobleaching and photoactivation of PSD subregions, we show that PSD-95 is nearly immobile within the PSD, and PSD subdomains can be maintained over long periods. We propose a flexible matrix model of the PSD based on stable molecular positioning of PSD-95 scaffolds.

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Section: Resultssupporting

confidence: 92%

“…5. It will be important to assess whether these or other oligomeric interactions of PSD proteins (22,39,40) confer stability to the complex as a whole or to subsets of proteins.…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Structural plasticity with preserved topology in the postsynaptic protein network

Blanpied

Kerr

Ehlers

2008

Proc. Natl. Acad. Sci. U.S.A.

119

104

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“…In γ-8-knockout mice, hippocampal synaptic transmission and plasticity are reduced (Rouach et al, 2005). Overexpression of the MAGUK PSD95 increases AMPAR-mediated transmission (Beique and Andrade, 2003;Ehrlich and Malinow, 2004;Nakagawa et al, 2004;Schnell et al, 2002), and PSD93 PSD95 double-knockout mice show a severe impairment in fast excitatory transmission (Elias et al, 2006). GRIP, NSF and PICK1 interact directly with the cytoplasmic tail of the GluR2 subunit of AMPARs (Kim et al, 2001;Luthi et al, 1999;Setou et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

The function of glutamatergic synapses is not perturbed by severe knockdown of 4.1N and 4.1G expression

Wozny

Breustedt

Wolk

et al. 2009

Journal of Cell Science

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AMPA-type glutamate receptors mediate fast excitatory synaptic transmission in the vertebrate brain. Their surface expression at synapses between neurons is regulated in an activity-dependent and activity-independent manner. The protein machinery that regulates synaptic targeting, anchoring and turnover of AMPA receptors consists of several types of specialized scaffolding proteins. The FERM domain scaffolding proteins 4.1G and 4.1N were previously suggested to act jointly in binding and regulating synaptic trafficking of the AMPA receptor subunits GluR1 and GluR4. To determine the functions of 4.1G and 4.1N in vivo, we generated a mutant mouse line that lacks 4.1G entirely and expresses 4.1N at 22% of wild-type levels. These mice had combined 4.1G and 4.1N protein expression in the hippocampus at 12% of wild-type levels (equivalent to 8-10% of combined GluR1 and GluR4 expression levels). They show a moderate reduction in synaptosomal expression levels of the AMPA receptor subunit GluR1 at 3 weeks of age, but no change in basic glutamatergic synaptic transmission and long-term potentiation in the hippocampus. Our study indicates that 4.1G and 4.1N do not have a crucial role in glutamatergic synaptic transmission and the induction and maintenance of long-term plastic changes in synaptic efficacy.

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“…The PSD-95-like subfamily of neuronal MAGUKs (PSD-MAGUKs) includes PSD-93, SAP102, and SAP97 (15)(16)(17). Comparative studies emphasize the remarkable similarities among PSD-MAGUKs in terms of protein-protein interactions (18,19) and overlapping functions in synaptic trafficking of AMPARs at mature synapses (20)(21)(22)(23)(24). On the other hand, the temporal coincidence of the early postnatal developmental switch from NR2B-to NR2A-NMDARs with the switch from SAP102 to PSD-95 expression raises the possibility that the two processes are related (25).…”

mentioning

confidence: 99%

Differential trafficking of AMPA and NMDA receptors by SAP102 and PSD-95 underlies synapse development

Elias

Apostolides

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

196

190

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The development of glutamatergic synapses involves changes in the number and type of receptors present at the postsynaptic density. To elucidate molecular mechanisms underlying these changes, we combine in utero electroporation of constructs that alter the molecular composition of developing synapses with dual whole-cell electrophysiology to examine synaptic transmission during two distinct developmental stages. We find that SAP102 mediates synaptic trafficking of AMPA and NMDA receptors during synaptogenesis. Surprisingly, after synaptogenesis, PSD-95 assumes the functions of SAP102 and is necessary for two aspects of synapse maturation: the developmental increase in AMPA receptor transmission and replacement of NR2B-NMDARs with NR2A-NMDARs. In PSD-95/PSD-93 double-KO mice, the maturational replacement of NR2B-with NR2A-NMDARs fails to occur, and PSD-95 expression fully rescues this deficit. This study demonstrates that SAP102 and PSD-95 regulate the synaptic trafficking of distinct glutamate receptor subtypes at different developmental stages, thereby playing necessary roles in excitatory synapse development.AMPAR and NMDAR trafficking ͉ membrane-associated guanylate kinase ͉ synaptogenesis ͉ postsynaptic density ͉ synaptic transmission A fundamental goal of developmental neurobiology is to identify the sequence of molecular events underlying excitatory synapse development, a process that can be divided into two distinct stages: synaptogenesis and synapse maturation. Synaptogenesis follows the specification of cell-to-cell contacts mediated by cell adhesion molecules (1, 2) and involves the initiation of chemical communication through the recruitment of pre-and postsynaptic proteins necessary for fast synaptic transmission (3, 4), such as AMPA receptors (AMPARs) and NMDA receptors (NMDARs). Synapse maturation is characterized by two functional events: an increase in the strength of AMPAR-mediated transmission (5, 6) and a switch in the subunit composition of synaptic NMDARs (7). NMDARs are composed of two obligatory NR1 subunits and two NR2 subunits, of which there are four members (NR2A-D) (8). NR2B-NMDARs are expressed during synaptogenesis and are replaced by NR2A-NMDARs during synapse maturation (9-11), a replacement that accounts for the developmental decrease in the NMDAR excitatory postsynaptic current (EPSC) decay time (12, 13) and the loss of sensitivity to the NR2B antagonist ifenprodil (14). The precise molecular mechanisms underlying the differential synaptic trafficking of AMPAR and NMDAR during developmental synaptogenesis and maturation remain largely unknown.PSD-95 is a member of a family of proteins collectively known as membrane-associated guanylate kinases (MAGUKs) (15-17). The PSD-95-like subfamily of neuronal MAGUKs (PSD-MAGUKs) includes PSD-93, SAP102, and SAP97 (15-17). Comparative studies emphasize the remarkable similarities among PSD-MAGUKs in terms of protein-protein interactions (18,19) and overlapping functions in synaptic trafficking of AMPARs at mature synapses (20-24). On the ot...

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Quaternary Structure, Protein Dynamics, and Synaptic Function of SAP97 Controlled by L27 Domain Interactions

Cited by 234 publications

References 63 publications

Structural plasticity with preserved topology in the postsynaptic protein network

Structural plasticity with preserved topology in the postsynaptic protein network

The function of glutamatergic synapses is not perturbed by severe knockdown of 4.1N and 4.1G expression

Differential trafficking of AMPA and NMDA receptors by SAP102 and PSD-95 underlies synapse development

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