SynGAP: a Synaptic RasGAP that Associates with the PSD-95/SAP90 Protein Family

Kim, Jee Hae; Liao, Dezhi; Lau, Lester F.; Huganir, Richard L.

doi:10.1016/s0896-6273(00)81008-9

Cited by 576 publications

(525 citation statements)

References 69 publications

(13 reference statements)

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“…synapses where it associates with PSD-95 and regulates cofilin activity [297][298][299] siRNA, exhibit increased actin polymerization and phospho-cofilin levels, and an increase in the synaptic strength and the in number of "mushroom" spines 297,301,305 , which is one of the notable classes of spine shape in addition to "thin", "stubby", and "branched". SYNGAP1…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Dendritic spine actin cytoskeleton in autism spectrum disorder

Joensuu¹,

Lanoue

Hotulainen

2018

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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Section: Accepted Manuscriptmentioning

confidence: 99%

Dendritic spine actin cytoskeleton in autism spectrum disorder

Joensuu¹,

Lanoue

Hotulainen

2018

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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“…Synaptophysin and bassoon are two major presynaptic proteins that are localized in or associated with presynaptic vesicles (Elferink and Scheller, 1995;Schoch and Gundelfinger, 2006;Shin, 2014;Wiedenmann and Franke, 1985). On the other hand, SynGAP and PSD95 are two major postsynaptic proteins that are enriched at postsynaptic sites of excitatory synapses, where they critically help organizing and strengthening excitatory receptor complexes and their associated signaling proteins (Kim et al, 1998;Kim and Sheng, 2004;Sheng and Hoogenraad, 2007). Microglia density was examined by 6 quantification of cells immunoreactive for the ionized calcium--binding adaptor molecule 1 (Iba1), whereas their activation status was assessed through the analysis of microglia morphology and cluster of differentiation 68 (CD68) immunoreactivity (Colton and Wilcock, 2010;Franco and Fernández--Suárez, 2015;Ransohoff and Perry, 2015).…”

Section: Introductionmentioning

confidence: 99%

Prenatal immune activation causes hippocampal synaptic deficits in the absence of overt microglia anomalies

Giovanoli

Weber‐Stadlbauer

Schedlowski

et al. 2016

Brain, Behavior, and Immunity

124

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Prenatal exposure to infectious or inflammatory insults can increase the risk of developing neuropsychiatric disorder in later life, including schizophrenia, bipolar disorder, and autism. These brain disorders are also characterized by pre-and postsynaptic deficits. Using a well-established mouse model of maternal exposure to the viral mimetic polyriboinosinic-polyribocytidilic acid [poly(I:C)], we examined whether prenatal immune activation might cause synaptic deficits in the hippocampal formation of pubescent and adult offspring. Based on the widely appreciated role of microglia in synaptic pruning, we further explored possible associations between synaptic deficits and microglia anomalies in offspring of poly(I:C)-exposed and control mothers. We found that prenatal immune activation induced an adult onset of presynaptic hippocampal deficits (as evaluated by synaptophysin and bassoon density). The early-life insult further caused postsynaptic hippocampal deficits in pubescence (as evaluated by PSD95 and SynGAP density), some of which persisted into adulthood. In contrast, prenatal immune activation did not change microglia (or astrocyte) density, nor did it alter their activation phenotypes. The prenatal manipulation did also not cause signs of persistent systemic inflammation. Despite the absence of overt glial anomalies or systemic inflammation, adult offspring exposed to prenatal immune activation displayed increased hippocampal IL-1 levels. Taken together, our findings demonstrate that age-dependent synaptic deficits and abnormal pro-inflammatory cytokine expression can occur during postnatal brain maturation in the absence of microglial anomalies or systemic inflammation. AbstractPrenatal exposure to infectious or inflammatory insults can increase the risk of developing neuropsychiatric disorder in later life, including schizophrenia, bipolar disorder, and autism. These brain disorders are also characterized by pre--and postsynaptic deficits.Using a well--established mouse model of maternal exposure to the viral mimetic polyriboinosinic--polyribocytidilic acid [poly(I:C)], we examined whether prenatal immune activation might cause synaptic deficits in the hippocampal formation of pubescent and adult offspring. Based on the widely appreciated role of microglia in synaptic pruning, we further explored possible associations between synaptic deficits and microglia anomalies in offspring of poly(I:C)--exposed and control mothers. We found that prenatal immune activation induced adult onset of presynaptic hippocampal deficits (as evaluated by synaptophysin and bassoon density). The early--life insult further caused postsynaptic hippocampal deficits in pubescence (as evaluated by PSD95 and SynGAP density), some of which persisted into adulthood. In contrast, prenatal immune activation did not change microglia (or astrocyte) density, nor did it alter their activation phenotypes. The prenatal manipulation did also not cause signs of persistent systemic inflammation. Despite the absence of overt glial a...

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“…The PDZ domain is a protein-interacting module (reviewed in Refs. 9 -12), and PSD-95/SAP90 binds the C termini of N-methyl-D-aspartate (NMDA) receptors, K ϩ channels, neuroligins, synGAP, and CRIPT through distinct PDZ domains to assemble these components at the synaptic junctions (13)(14)(15)(16)(17)(18). PSD-95/SAP90 interacts with SAP90/PSD-95-associated protein (SAPAP) (also called GK-associated protein and hDLGassociated protein) (19 -21), and a recently identified protein, BEGAIN (brain-enriched guanylate kinase-interacting protein) via the GK domain (22).…”

mentioning

confidence: 99%

MAGUIN, a Novel Neuronal Membrane-associated Guanylate Kinase-interacting Protein

Yao¹,

Hata²,

Ide³

et al. 1999

Journal of Biological Chemistry

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Postsynaptic density (PSD)-95/Synapse-associated protein (SAP) 90 and synaptic scaffolding molecule (S-SCAM) are neuronal membrane-associated guanylate kinases. Because PSD-95/SAP90 and S-SCAM function as synaptic scaffolding proteins, identification of ligands for these proteins is important to elucidate the structure of synaptic junctions. Here, we report a novel protein interacting with the PDZ domains of PSD-95/SAP90 and S-SCAM and named it MAGUIN-1 (membrane-associated guanylate kinase-interacting protein-1). MAGUIN-1 has one sterile ␣ motif, one PDZ, and one plekstrin homology domain. MAGUIN-1 is localized at the plasma membrane via the plekstrin homology domain and the C-terminal region and interacts with PSD-95/SAP90 and S-SCAM via a C-terminal PDZ domainbinding motif. MAGUIN-1 has a short isoform, MAGUIN-2, which lacks a PDZ domain-binding motif. MAGUINs are expressed in neurons and localized in the cell body and neurites and are coimmunoprecipitated with PSD-95/ SAP90 and S-SCAM from rat crude synaptosome. MAGUIN-1 may play an important role with PSD-95/SAP90 and S-SCAM to assemble the components of synaptic junctions.Synaptic junctions are interneuronal cell-cell junctions differentiated for neurotransmission. Neurotransmitters are released from the synaptic vesicles into the synaptic cleft and bind to the receptors accumulated at the postsynapse, opening the ion channels and generating the second messengers involved in synaptic plasticity (reviewed in Ref. 1). The components required for this process are organized at the synaptic junctions to play specific roles in felicitous orders. Several scaffolding proteins are reported to be involved in the assembly of components of synaptic junctions (reviewed in Refs. 2-6). Postsynaptic density (PSD) 1 -95/synapse-associated protein (SAP) 90 has three PSD-95/Dlg-A/ZO-1 (PDZ) domain, one Src homology 3 domain, and one guanylate kinase (GK) domain (7,8). The PDZ domain is a protein-interacting module (reviewed in Refs. 9 -12), and PSD-95/SAP90 binds the C termini of N-methyl-D-aspartate (NMDA) receptors, K ϩ channels, neuroligins, synGAP, and CRIPT through distinct PDZ domains to assemble these components at the synaptic junctions (13-18). PSD-95/SAP90 interacts with SAP90/PSD-95-associated protein (SAPAP) (also called GK-associated protein and hDLGassociated protein) (19 -21), and a recently identified protein, BEGAIN (brain-enriched guanylate kinase-interacting protein) via the GK domain (22). Glutamate receptor-interacting protein has seven PDZ domains and binds ␣ amino-3-hydroxy-5-methyl-4-isoxazaole propionic acid receptors via the fourth and fifth PDZ domains (23). The ligands for other PDZ domains of glutamate receptor-interacting protein have not been so far reported. Synaptic scaffolding molecule (S-SCAM) was originally identified as a SAPAP-interacting protein (24). We have first reported that S-SCAM has one GK, two WW, and five PDZ domains (24). The GK domain of S-SCAM is shorter than that of PSD-95/SAP90. The WW domain is a protein-interacting modul...

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SynGAP: a Synaptic RasGAP that Associates with the PSD-95/SAP90 Protein Family

Cited by 576 publications

References 69 publications

Dendritic spine actin cytoskeleton in autism spectrum disorder

Dendritic spine actin cytoskeleton in autism spectrum disorder

Prenatal immune activation causes hippocampal synaptic deficits in the absence of overt microglia anomalies

MAGUIN, a Novel Neuronal Membrane-associated Guanylate Kinase-interacting Protein

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