Mutagenesis Reveals a Role for ABP/GRIP Binding to GluR2 in Synaptic Surface Accumulation of the AMPA Receptor

Osten, Pavel; Khatri, Latika; Perez, Joey L.; Köhr, Georg; Giese, Günter; Daly, Christopher; Schulz, Torsten; Wensky, Allen; Lee, Laveria M.; Ziff, Edward B.

doi:10.1016/s0896-6273(00)00039-8

Cited by 277 publications

(257 citation statements)

References 39 publications

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“…particular postsynaptic roles. For example, Pick 1 and GRIP1, which both interact with the C-terminal terminal of the AMPA receptor subunits, GluR2/3, are involved in their internalization and synaptic stabilization (Dong et al 1999;Dev et al 1999;Chung et al 2000;Daw et al 2000;El-Husseini et al 2000;Osten et al 2000). SAP97 interacts with the AMPA receptor subunit GluR1 and stabilizes receptor protein expression at postsynaptic sites (Leonard et al 1998;Jourdi et al 2001;Sans et al 2001).…”

Section: Discussionmentioning

confidence: 99%

Selective reduction of a PDZ protein, SAP‐97, in the prefrontal cortex of patients with chronic schizophrenia

Toyooka

Iritani

Makifuchi

et al. 2002

Journal of Neurochemistry

111

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Many postsynaptic density proteins carrying postsynaptic density-95/discs large/zone occludens-1 (PDZ) domain(s) interact with glutamate receptors to control receptor dynamics and synaptic plasticity. Here we examined the expression of PDZ proteins, synapse-associated protein (SAP) 97, postsynaptic density (PSD)-95, chapsyn-110, GRIP1 and SAP102, in post-mortem brains of schizophrenic patients and control subjects, and evaluated their contribution to schizophrenic pathology. Among these PDZ proteins, SAP97 exhibited the most marked change: SAP97 protein levels were decreased to less than half that of the control levels specifically in the prefrontal cortex of schizophrenic patients. In parallel, its binding partner, GluR1, similarly decreased in the same brain region. The correlation between SAP97 and GluR1 levels in control subjects was, however, altered in schizophrenic patients. SAP102 levels were also significantly reduced in the hippocampus of schizophrenic patients, but this reduction was correlated with sample storage time and post-mortem interval. There were no changes in the levels of the other PDZ proteins in any of the regions examined. In addition, neuroleptic treatment failed to mimic the SAP97 change. These findings suggest that a phenotypic loss of SAP97 is associated with the postsynaptic impairment in prefrontal excitatory circuits of schizophrenic patients. Keywords: chapsyn-110, GRIP1, PSD-95, psychosis, SAP102, SAP97. Address correspondence and reprint requests to Hiroyuki Nawa, Department of Molecular Biology, Brain Research Institute, Niigata University, Asahimachi-dori 1-757, Niigata 951-8585, Japan. E-mail: hnawa@bri.niigata-u.ac.jpAbbreviations used: ABP, AMPA receptor-binding protein; AMPA, a-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid; BDNF, brainderived neurotrophic factor; DTT, dithiothreitol; LPT, long-term potentiation; NSE, neuron-specific enolase; PAGE, polyacrylamide gel electrophoresis; PDZ, PSD-95/discs large/zone occludens-1; PVDF, polyvinylidene difluoride; PSD, postsynaptic density; SAP, synapseassociated protein; SDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

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Section: Discussionmentioning

confidence: 99%

Selective reduction of a PDZ protein, SAP‐97, in the prefrontal cortex of patients with chronic schizophrenia

Toyooka

Iritani

Makifuchi

et al. 2002

Journal of Neurochemistry

111

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“…Association of a glutamate receptor-interacting protein called GRIP1 with the GluR2 subunit of the AMPA receptor is critically important for synaptic targeting and clustering of the receptor (Dong et al, 1999;Osten et al, 2000). The Cterminal tail of GluR2 binds to the fourth and fifth PDZ domain (PDZ4-PDZ5) module of GRIP1; but, surprisingly, cannot bind the isolated PDZ4 and PDZ5 domains (Zhang et al, 2001).…”

Section: Structural Integration Of Multi-domain Modulesmentioning

confidence: 99%

Extensions of PDZ domains as important structural and functional elements

et al. 2010

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ABSTRACT'Divide and conquer' has been the guiding strategy for the study of protein structure and function. Proteins are divided into domains with each domain having a canonical structural definition depending on its type. In this review, we push forward with the interesting observation that many domains have regions outside of their canonical definition that affect their structure and function; we call these regions 'extensions'. We focus on the highly abundant PDZ (PSD-95, DLG1 and ZO-1) domain. Using bioinformatics, we find that many PDZ domains have potential extensions and we developed an openly-accessible website to display our results (http:// bcz102.ust.hk/pdzex/). We propose, using well-studied PDZ domains as illustrative examples, that the roles of PDZ extensions can be classified into at least four categories: 1) protein dynamics-based modulation of target binding affinity, 2) provision of binding sites for macro-molecular assembly, 3) structural integration of multi-domain modules, and 4) expansion of the target ligand-binding pocket. Our review highlights the potential structural and functional importance of domain extensions, highlighting the significance of looking beyond the canonical boundaries of protein domains in general.

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“…Removal of the PDZ binding site from GluR2 reduces the accumulation of AMPAR levels at the synapse 42 . Moreover, disruption of the interaction between GluR2 and GluR3 and PDZ domains has been reported to block LTD in the hippocampus 43 and cerebellum 44 .…”

Section: When Do Ampars Take a Break?mentioning

confidence: 99%

Restless AMPA receptors: implications for synaptic transmission and plasticity

Lüscher

Frerking

2001

Trends in Neurosciences

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A central assumption in neurobiology holds that changes in the strength of individual synapses underlie changes in behavior. This concept is widely accepted in the case of learning and memory where LTP and LTD are the most compelling cellular models. It is therefore of great interest to understand, on a molecular level, how the brain regulates the strength of neuronal connections. We review a large body of evidence in support of the very straightforward regulation of synaptic strength by changing the number of postsynaptic receptors, and discuss the molecular machinery required for insertion and removal of AMPA receptors.The hypothesis that insertion of AMPA receptors (AMPARs) underlies the increase of synaptic strength associated with LTP was put forward almost 20 years ago 1 , but was largely ignored until the mid-1990s, resurfacing with quantal analysis of LTP (Ref. 2 ). However, only recently has it become the subject of direct experimental scrutiny.The spark for the myriad of research published in the past few years in the field was experiments conducted independently by two groups 3,4 , in which single connections between CA3 axons and CA1 pyramidal cells in acute hippocampal slices were functionally isolated and in some cases yielded only responses from NMDA receptors (NMDARs) and not AMPARs. Inducing LTP, however, caused the appearance of AMPAR mediated excitatory postsynaptic currents (EPSCs). This led to the proposal that a fraction of 'silent' synapses contain only NMDARs, and thus are functionally inactive at normal resting potential, but maintain the capability to undergo LTP, which would be expressed by AMPAR insertion. Although alternative explanations for these results have been proposed 5,6 , synapses with NMDARs but not AMPARs have now been directly identified anatomically in cultured hippocampal neurons using immunofluorescence 7,8 and with immuno-gold preparations visualized by electron microscopy in hippocampal slices 9-11 .AMPARs move from the cytoplasm to the surface and back again Constitutive recyclingIf LTP expression is caused by postsynaptic AMPAR insertion, it must be the case that AMPARs can be inserted into and removed from the postsynaptic membrane on a relatively rapid time scale. To test this experimentally, CA1 pyramidal cells in acute hippocampal slices * Christian.Luscher@medecine.unige.ch.

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Mutagenesis Reveals a Role for ABP/GRIP Binding to GluR2 in Synaptic Surface Accumulation of the AMPA Receptor

Cited by 277 publications

References 39 publications

Selective reduction of a PDZ protein, SAP‐97, in the prefrontal cortex of patients with chronic schizophrenia

Selective reduction of a PDZ protein, SAP‐97, in the prefrontal cortex of patients with chronic schizophrenia

Extensions of PDZ domains as important structural and functional elements

Restless AMPA receptors: implications for synaptic transmission and plasticity

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