GRIP: a synaptic PDZ domain-containing protein that interacts with AMPA receptors

Dong, Hualing; O’Brien, Richard; Fung, Eric T.; Lanahan, Anthony A.; Worley, Paul F.; Huganir, Richard L.

doi:10.1038/386279a0

Cited by 820 publications

(635 citation statements)

References 29 publications

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“…Furthermore, another PDZ domain-containing GluA2/3 interacting protein, GRIP1, has also been implicated in this process. GRIP1 is thought to anchor AMPARs at synapses 106 . Peptides that block the GRIP1-GluA2/3 interaction destabilize GluA2-lacking CP-AMPARs at synapses, and synaptic activity reduces the interaction of GRIP1 with CP-AMPARs 104 .…”

Section: Mechanisms Of Subunit-specific Traffickingmentioning

confidence: 99%

Synaptic AMPA receptor composition in development, plasticity and disease

2016

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General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. PrefaceAMPARs are assemblies of four core subunits, GluA1-4, that mediate most fast excitatory neurotransmission. The component subunits determine the functional properties of AMPARs and the prevailing view is that the subunit composition also determines AMPAR trafficking, which is dynamically regulated during development, synaptic plasticity, and in response to neuronal stress in disease. Recently, the subunit-dependence of AMPAR trafficking has been questioned leading to a reappraisal of the field. Here we review what is known, uncertain, conjectured and unknown about the roles of individual subunits and how they impact on AMPAR assembly, trafficking and function under normal and pathological conditions. IntroductionAMPA receptors (AMPARs) are a subtype of ionotropic glutamate receptors that are the 'work-horses' of fast excitatory neurotransmission in the CNS. Developmentallyand activity-regulated changes in the numbers and properties of AMPARs localized at the postsynaptic membrane are essential for excitatory synapse formation, stabilization, synaptic plasticity and neural circuit formation. Consequently, the logistics of the delivery, retention and removal of individual AMPARs with defined subunit compositions at specific synapses is highly complex. A typical cortical or hippocampal pyramidal neuron contains on the order of 10,000 synapses and the AMPARs at each synapse are independently and dynamically regulated in response to developmental cues, synaptic activity and environmental stresses. Furthermore, defects in the processes that control AMPAR assembly, trafficking and synaptic expression are intimately linked to psychiatric and neurological conditions, and also with cognitive decline in neurodegenerative diseases. Remarkable progress has been achieved in understanding how AMPAR trafficking, is orchestrated by a large array of AMPAR interacting proteins. These studies have established a set of hierarchical subunit-specific rules that control AMPAR trafficking under basal and activity-dependent conditions. Furthermore, there has been a growing appreciation that subunit composition can tune the properties of AMPARs to specific conditions. Nonetheless, how AMPARs comprising different subunits are differentially trafficked to control synaptic development, stabilisation and plasticity is a key unanswered question. Here, we provide an overview of the current state of knowledge of subunit-specific AMPAR trafficking and outline what we believe to be the key unresolved questions in the field. 2 Subunit-specific traffickingMost AMPARs are heterotetrameric assemblies of combinations of the subunits GluA1, GluA2, GluA3 and GluA4. AMPARs are expressed in both neurons and glia throughout the CNS 1 and have a turnover time of between 10 hours and 2 days depending on the type of neuron and developmental stage 2,3 . Each subunit has an identical membrane topology and c...

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Section: Mechanisms Of Subunit-specific Traffickingmentioning

confidence: 99%

Synaptic AMPA receptor composition in development, plasticity and disease

2016

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“…To date, studies of AMPA receptor trafficking have focused on the presence or absence of AMPA receptors at synaptic sites, or on internal versus surface expression [3][4][5][6][7][8][9][10][15][16][17][18] . However, the multiple subunits of AMPA receptors interact differentially with diverse cytoplasmic proteins including GRIP/ABP, PICK1, NSF and SAP97, all of which have been implicated in synaptic targeting of AMPA receptors 3,5,17,[19][20][21][22][23][24][25][26][27] . The diversity of AMPA receptor protein interactions, and their regulation by phosphorylation 28 , suggest that AMPA receptor trafficking is likely to be regulated by varied mechanisms.…”

Section: Articlesmentioning

confidence: 99%

Distinct molecular mechanisms and divergent endocytotic pathways of AMPA receptor internalization

et al. 2000

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articlesThe AMPA class of ionotropic glutamate receptors mediates most of the fast excitatory synaptic transmission in mammalian brain 1 . Changing the responsiveness of postsynaptic AMPA receptors offers a powerful way to regulate excitatory synaptic transmission. Among the mechanisms proposed for modification of AMPA receptor activity, one of the simplest is a change in the number of AMPA receptors in the postsynaptic membrane. Studies suggest that AMPA receptors can move in and out of the postsynaptic membrane on a rapid time scale (for review, see ref.2). Moreover, changes in postsynaptic membrane trafficking or in synaptic targeting of AMPA receptors have been correlated with alterations in synaptic efficacy [2][3][4][5][6][7][8][9] .In developing neurons in culture, synaptic expression of AMPA receptors is modulated over a period of days by relative levels of AMPA and NMDA receptor activity [10][11][12] . Mature neurons in culture also exhibit slow changes in synaptic AMPA receptor expression in response to chronic changes in endogenous activity 9,13,14 . On a faster time scale, induction of long-term depression (LTD) or acute application of AMPA or insulin can induce a loss of AMPA receptors from the cell surface of cultured hippocampal neurons within minutes 3,6,9,15 . Conversely, induction of long-term potentiation (LTP) and activation of CaMKII are correlated with a rapid recruitment of AMPA receptors to the postsynaptic membrane 5,8 . Thus, the synaptic content of AMPA receptors can change bidirectionally on a fast time scale and result in altered synaptic transmission.Little is known about the cell biological pathways or molecular mechanisms of postsynaptic AMPA receptor trafficking. To date, studies of AMPA receptor trafficking have focused on the presence or absence of AMPA receptors at synaptic sites, or on internal versus surface expression [3][4][5][6][7][8][9][10][15][16][17][18] . However, the multiple subunits of AMPA receptors interact differentially with diverse cytoplasmic proteins including GRIP/ABP, PICK1, NSF and SAP97, all of which have been implicated in synaptic targeting of AMPA receptors 3,5,17,[19][20][21][22][23][24][25][26][27] . The diversity of AMPA receptor protein interactions, and their regulation by phosphorylation 28 , suggest that AMPA receptor trafficking is likely to be regulated by varied mechanisms.Here we report that multiple distinct pathways exist for AMPA receptor endocytosis in cultured hippocampal neurons. We have quantified a basal rate of AMPA receptor internalization, which can be enhanced by a variety of stimuli including synaptic activity, ligand binding to AMPA receptors, insulin and calcium influx. Different internalizing stimuli use distinct intracellular signaling mechanisms, different endosomal sorting pathways and distinct sequence determinants within AMPA receptor subunits to effect AMPA receptor endocytosis. RESULTS Ligand-dependent endocytosis of AMPA receptorsTranslocation of AMPA receptors from cell surface to intracellular compartments was visu...

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“…Similarly, a group of PDZ molecules interacting with a-amino-3-hydroxy-5-methyl-4-isoxzolepropionic acid (AMPA)-type glutamate receptors has been identified. SAP97 associates with the C-terminal motif of glutamate receptor 1 (GluR1) (Leonard et al 1998;Sans et al 2001) and GRIP, AMPA receptorbinding protein (ABP), stargazin and Pick1 bind to the C-terminal motif of GluR2/3 (Dong et al 1997;Srivastava et al 1998;Dong et al 1999;Xia et al 1999;Chen et al 2000). The PDZ domain of PSD-95 and other proteins also interacts with a variety of other signaling molecules at synapses (O'Brien et al 1998;Nagano et al 1998;Fanning and Anderson 1999).…”

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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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GRIP: a synaptic PDZ domain-containing protein that interacts with AMPA receptors

Cited by 820 publications

References 29 publications

Synaptic AMPA receptor composition in development, plasticity and disease

Synaptic AMPA receptor composition in development, plasticity and disease

Distinct molecular mechanisms and divergent endocytotic pathways of AMPA receptor internalization

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

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