nRap GEP: A Novel Neural GDP/GTP Exchange Protein for Rap1 Small G Protein That Interacts with Synaptic Scaffolding Molecule (S-SCAM)

Ohtsuka, Toshihisa; Hata, Yoshinobu; Ide, Nobuyuki; Yasuda, Takeo; Inoue, Eiji; Inoue, Takahiro; Mizoguchi, Akira; Takai, Yoshimi

doi:10.1006/bbrc.1999.1619

Cited by 97 publications

(88 citation statements)

References 41 publications

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“…49 SynGaP binds to the PDZ domains of scaffold protein PSD-95. 46,47 SPar is also associated with PSD-95 via a guanylate kinase domain interaction.…”

Section: Discussionmentioning

confidence: 99%

Plk2 Raps up Ras to subdue synapses

2011

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We recently identified the activityinducible protein kinase Plk2 as a novel overseer of the balance between Ras and Rap small GTPases. Plk2 achieves a profound level of regulatory control by interacting with and phosphorylating at least four Ras and Rap guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs). Combined, these actions result in synergistic suppression of Ras and hyperstimulation of Rap signaling. Perturbation of Plk2 function abolished homeostatic adaptation of synapses to enhanced activity and impaired behavioral adaptation in various learning tasks, indicating that this regulation was critical for maintaining appropriate Ras/Rap levels. These studies provide insights into the highly cooperative nature of Ras and Rap regulation in neurons. However, different GEF and GAP substrates of Plk2 also controlled specific aspects of dendritic spine morphology, illustrating the ability of individual GAPs/GEFs to assemble microdomains of Ras and Rap signaling that respond to different stimuli and couple to distinct output pathways.

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“…49 SynGaP binds to the PDZ domains of scaffold protein PSD-95. 46,47 SPar is also associated with PSD-95 via a guanylate kinase domain interaction.…”

Section: Discussionmentioning

confidence: 99%

Plk2 Raps up Ras to subdue synapses

2011

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“…PDZ-GEF1 binds to ␤- catenin and to the scaffold proteins MAGI-1 and MAGI-2, which both interact with ␤-catenin as well (Dobrosotskaya and James, 2000;Kawajiri et al, 2000;Mino et al, 2000;Ohtsuka et al, 1999;Sakurai et al, 2006). Both the presence of MAGI-1 at endothelial cell-cell junctions and its ␤-catenin binding site are required for cell-cell-contact-induced Rap1 activation (Sakurai et al, 2006).…”

Section: Activation Of Rap1 By Cell-cell Contactsmentioning

confidence: 99%

Rap1: a key regulator in cell-cell junction formation

Kooistra

Dubé

Bos

2007

Journal of Cell Science

294

236

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Rap1 is a Ras-like small GTPase that is activated by many extracellular stimuli and strongly implicated in the control of integrin-mediated cell adhesion. Recent evidence indicates that Rap1 also plays a key role in formation of cadherin-based cell-cell junctions. Indeed, inhibition of Rap1 generates immature adherens junctions, whereas activation of Rap1 tightens cell-cell junctions. Interestingly, Rap1 guanine nucleotide exchange factors, such as C3G and PDZ-GEF, are directly linked to E-cadherin or to other junction proteins. Furthermore, several junction proteins, such as afadin/AF6 and proteins controlling the actin cytoskeleton, function as effectors of Rap1. These findings point to a role of Rap1 in spatial and temporal control of cell-cell junction formation.

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“…Neuroligins are clustered by MAGI-2 , and the C terminus of neuroligin-1 interacts specifically with PDZ domain 1 (Hirao et al, 1998). Other proteins interacting with PDZ domain 1 include the ␤1-adrenergic receptor (Xu et al, 2001) and neural GDP/ GTP exchange protein Rapgef2 (Ohtsuka et al, 1999). Measuring the relative access of TARPs and other proteins to different PDZ domains of MAGI-2 in vivo will be an important topic of future investigation.…”

Section: Regional Specificity Of Tarp-magi-2 Interactions In Brainmentioning

confidence: 99%

“…(phosphatase and tensin homolog), RapGEF2 (Rap guanine nucleotide exchange factor 1), and SAP-associated protein (Hirao et al, 1998;Wood et al, 1998;Ide et al, 1999;Ohtsuka et al, 1999;Yao et al, 1999;Shoji et al, 2000;Wu et al, 2000;Xu et al, 2001;Nishimura et al, 2002;Pfister et al, 2003;Hirabayashi et al, 2004;Iida et al, 2004;Kimura et al, 2004;Shi et al, 2004;Kremerskothen et al, 2006).…”

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confidence: 99%

Stargazin and Other Transmembrane AMPA Receptor Regulating Proteins Interact with Synaptic Scaffolding Protein MAGI-2 in Brain

et al. 2006

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MAGI-2 [also known as S-SCAM (synaptic scaffolding molecule)] is a multi-PDZ domain scaffolding protein that interacts with several different ligands in brain, including PTEN (phosphatase and tensin homolog), dasm1(dendrite arborization and synapse maturation 1), dendrin, axin, ␤-and ␦-catenin, neuroligin, hyperpolarization-activated cation channels, ␤1-adrenergic receptors, and NMDA receptors. We confirmed that MAGI-2 coimmunoprecipitated with stargazin in vivo from mouse cerebral cortex and used in vitro assays to localize the interaction to the C-terminal -TTPV amino acid motif of stargazin and the PDZ1, PDZ3, and PDZ5 domains of MAGI-2. Expression of stargazin recruited MAGI-2 to cell membranes and cell-cell contact sites in transfected HEK-293T cells dependent on the presence of the stargazin -TTPV motif. These experiments identify MAGI-2 as a strong candidate for linking TARP/AMPA receptor complexes to a wide range of other postsynaptic molecules and pathways and advance our knowledge of protein interactions at mammalian CNS synapses.

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nRap GEP: A Novel Neural GDP/GTP Exchange Protein for Rap1 Small G Protein That Interacts with Synaptic Scaffolding Molecule (S-SCAM)

Cited by 97 publications

References 41 publications

Plk2 Raps up Ras to subdue synapses

Plk2 Raps up Ras to subdue synapses

Rap1: a key regulator in cell-cell junction formation

Stargazin and Other Transmembrane AMPA Receptor Regulating Proteins Interact with Synaptic Scaffolding Protein MAGI-2 in Brain

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