Localization of Postsynaptic Density-93 to Dendritic Microtubules and Interaction with Microtubule-Associated Protein 1A

Brenman, Jay E.; Topinka, Jan; Cooper, Edward C.; McGee, Aaron W.; Rosen, Joel M.; Milroy, Toni; Ralston, Henry J.; Bredt, David S.

doi:10.1523/jneurosci.18-21-08805.1998

Cited by 188 publications

(151 citation statements)

References 62 publications

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“…For example, the GK domain plays an essential role in forming the structural arrangement of SAP97, which is needed for Kir3.2c sensitization to G proteins by SAP97. It was reported that the GK domain bound to SH3 but not any PDZ domains within PSD-95 as well as DLG molecules (Brenman et al, 1998;McGee and Bredt, 1999). This intramolecular interaction between SH3 and GK domains may be a candidate for the mechanism of the structural arrangement of SAP97.…”

Section: Discussionmentioning

confidence: 90%

“…The anchoring proteins also act as scaffolds by arranging signal molecules in a certain order that is determined by the specific binding of signal molecules to different PDZ domains. Recent studies have revealed that the GK domain of PSD/SAP family proteins, although it has no guanylate kinase activity , acts as a binding domain for SAPAPs/GKAP/PAP Satoh et al, 1997;Takeuchi et al, 1997), MAP1A (Brenman et al, 1998), BEGAIN (Deguchi et al, 1998) or the kainate receptor (Garcia et al, 1998). However, the functional role of the GK domain has remained largely unclarified.…”

Section: Discussionmentioning

confidence: 99%

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Anchoring proteins confer G protein sensitivity to an inward-rectifier K+ channel through the GK domain

et al. 2000

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Anchoring proteins cluster receptors and ion channels at postsynaptic membranes in the brain. They also act as scaffolds for intracellular signaling molecules including synGAP and NO synthase. Here we report a new function for intracellular anchoring proteins: the regulation of synaptic ion channel function. A neuronal G protein-gated inwardly rectifying K ϩ channel, Kir3.2c, can not be activated either by M 2 -muscarinic receptor stimulation or by G βγ overexpression. When coexpressed with SAP97, a member of the PSD/ SAP anchoring protein family, the channel became sensitive to G protein stimulation. Although the C-terminus of Kir3.2c bound to the second PDZ domain of SAP97, functional analyses revealed that the guanylate kinase (GK) domain of SAP97 is crucial for sensitization of the Kir3.2c channel to G protein stimulation. Furthermore, SAPAP1/GKAP, which binds specifically to the GK domain of membrane-associated guanylate kinases, prevented the SAP97-induced sensitization. The function of a synaptic ion channel can therefore be controlled by a network of various intracellular proteins.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Anchoring proteins confer G protein sensitivity to an inward-rectifier K+ channel through the GK domain

et al. 2000

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“…Each domain in the SAP subfamily of MAGUKs is highly conserved and has been shown to be a site of protein-protein interaction: PDZ domains bind voltage-and ligand-gated ion channels (3,9); SH3 domains interact with proline-rich, PXXPR-like sequences (3,4,10) as well as with the GK domain of CASK (11); GKAP/SAPAP (12)(13)(14), the microtubule-associated protein MAP1A (15), the brain-enriched guanylate kinase associated protein (BEGAIN) (16), and the guanylate kinase associated kinesin GAKIN (17) are interaction partners of the GK domain. The GK domain is catalytically inactive, although structurally closely related to authentic guanylate kinases as we have shown in previous work (18,19).…”

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confidence: 99%

Formation of Complexes between Ca2+·Calmodulin and the Synapse-associated Protein SAP97 Requires the SH3 Domain-Guanylate Kinase Domain-connecting HOOK Region

Paarmann

Spangenberg

Lavie

et al. 2002

Journal of Biological Chemistry

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Mammalian synapse-associated protein SAP97, a structural and functional homolog of Drosophila Dlg, is a membrane-associated guanylate kinase (MAGUK) that is present at pre-and postsynaptic sites as well as in epithelial cell-cell contact sites. It is a multidomain scaffolding protein that shares with other members of the MAGUK protein family a characteristic modular organization composed of three sequential protein interaction motifs known as PDZ domains, followed by an Src homology 3 (SH3) domain, and an enzymatically inactive guanylate kinase (GK)-like domain. Specific binding partners are known for each domain, and different modes of intramolecular interactions have been proposed that particularly involve the SH3 and GK domains and the so-called HOOK region located between these two domains. We identified the HOOK region as a specific site for calmodulin binding and studied the dynamics of complex formation of recombinant calmodulin and SAP97 by surface plasmon resonance spectroscopy. Binding of various SAP97 deletion constructs to immobilized calmodulin was strictly calciumdependent. From the rate constants of association and dissociation we determined an equilibrium dissociation constant K d of 122 nM for the association of calcium-saturated calmodulin and a SAP97 fragment, which encompassed the entire SH3-HOOK-GK module. Comparative structure-based sequence analysis of calmodulin binding regions from various target proteins predicts variable affinities for the interaction of calmodulin with members of the MAGUK protein family. Our findings suggest that calmodulin could regulate the intramolecular interaction between the SH3, HOOK, and GK domains of SAP97.Membrane-associated guanylate kinase homologs (MAGUKs) 1 have been implicated in the assembly of synapses and tight junctions. These are multidomain proteins consisting of one or more PDZ domains, an Src homology 3 (SH3) domain, and a guanylate kinase (GK)-like domain (for reviews, see Refs. 1-4). Rat SAP97 belongs to the MAGUK subfamily comprising Drosophila Dlg, SAP97/hDlg, SAP90/PSD-95, SAP102/NE-Dlg, and PSD93/Chapsyn110. SAP97 has earlier been reported to be presynaptic (5), but it has recently been shown also to be present at postsynaptic sites in cerebral cortex (6); it is found both at the post-synaptic density (PSD) region and in the cytoplasm of hippocampal synapses, suggesting a role for SAP97 in ionotropic glutamate receptor trafficking (7). Recently it was discovered that SAP97, via its guanylate kinase (GK)-like domain, directly regulates the function of an inwardly rectifier potassium channel (8). In addition to its crucial role as a scaffolding protein in neuronal cells, SAP97 is an essential component of the basolateral membrane cytoskeleton in a variety of epithelial cells (5).Each domain in the SAP subfamily of MAGUKs is highly conserved and has been shown to be a site of protein-protein interaction: PDZ domains bind voltage-and ligand-gated ion channels (3, 9); SH3 domains interact with proline-rich, PXXPR-like sequences (3, 4, 10) as w...

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“…The GK domain of the PSD-95 family of MAGUKs interacts with the GKAP/SAPAP/DAP family of postsynaptic density proteins Naisbitt et al, 1997;Takeuchi et al, 1997), BEGAIN (Deguchi et al, 1998), and MAP1A (Brenman et al, 1998). GKAP in turn interacts with a novel postsynaptic scaffold protein termed Shank Naisbitt et al, 1999;Tu et al, 1999).…”

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confidence: 99%

An Intramolecular Interaction between Src Homology 3 Domain and Guanylate Kinase-Like Domain Required for Channel Clustering by Postsynaptic Density-95/SAP90

et al. 2000

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Members of the postsynaptic density-95 (PSD-95)/SAP90 family of membrane-associated guanylate kinase (MAGUK) proteins function as multimodular scaffolds that organize proteinsignaling complexes at neuronal synapses. MAGUK proteins contain PDZ, Src homology 3 (SH3), and guanylate kinase (GK)-like domains, all of which can function as sites for specific protein-protein interactions. We report here a direct proteinprotein interaction between the SH3 domain and the GK region in the PSD-95 family of MAGUKs. The SH3 domain of the PSD-95 family appears to have an atypical binding specificity, because the classical SH3 binding (-P-X-X-P-) motif is absent from the GK domain. Although SH3-GK binding can occur in either an intramolecular or intermolecular manner, the intramolecular mode is preferred, possibly because of additional tertiary interactions available when the SH3 and GK domains are adjacent in the same polypeptide. Mutations disrupting the intramolecular SH3-GK interaction do not interfere with PSD-95 association with the K ϩ channel Kv1.4 or with the GK domain-binding protein GKAP. The same mutations, however, inhibit the clustering of Kv1.4 by PSD-95, suggesting that the intramolecular SH3-GK interaction may modulate the clustering activity of PSD-95. Key words: PDZ domain; ion channel clustering; postsynaptic density; Src tyrosine kinase; polyproline helix; disks largeSynaptic transmission in neuronal synapses requires the proper organization of ion channels, neurotransmitter receptors, and signaling molecules in the synaptic junction. An emerging theme for the micro-organization of synapses is that functionally coupled proteins are placed in close proximity to each other via their interactions with scaffold proteins. The PSD-95 family of membrane-associated guanylate kinases (MAGUKs) plays such a role at postsynaptic sites of glutamatergic synapses by interacting with a variety of ion channels, receptors, cytoskeletal components, and intracellular signaling proteins (Sheng and Wyszynski, 1997;Ziff, 1997;Craven and Bredt, 1998;Kennedy, 1998;O'Brien et al., 1998).The PSD-95 family of proteins (PSD-95/SAP90, SAP97/hdlg, chapsyn-110/PSD-93, and SAP102) share a common domain organization, consisting of three PDZ domains in their N-terminal half, a central Src homology 3 (SH3) domain, and a guanylate kinase (GK) domain at their C terminus. The PDZ domains of PSD-95 family proteins interact with the C terminal sequence motif (consensus -X-T/S-X-V) found in a variety of membrane and intracellular proteins, including Shaker K ϩ channels, NMDA receptors, and SynGAP (Kim et al., 1995Kornau et al., 1995;Doyle et al., 1996;Chen et al., 1998). In addition, PSD-95 binds to neuronal nitric oxide synthase (nNOS) through a PDZ-PDZ/␤-finger interaction (Brenman et al., 1996a;Hillier et al., 1999). In vitro and in vivo evidence suggests that these PDZmediated interactions are involved in the clustering of specific membrane proteins at synaptic sites (Kim et al., 1995Thomas et al., 1997).The GK domain of the PSD-95 family of MA...

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Localization of Postsynaptic Density-93 to Dendritic Microtubules and Interaction with Microtubule-Associated Protein 1A

Cited by 188 publications

References 62 publications

Anchoring proteins confer G protein sensitivity to an inward-rectifier K+ channel through the GK domain

Anchoring proteins confer G protein sensitivity to an inward-rectifier K+ channel through the GK domain

Formation of Complexes between Ca2+·Calmodulin and the Synapse-associated Protein SAP97 Requires the SH3 Domain-Guanylate Kinase Domain-connecting HOOK Region

An Intramolecular Interaction between Src Homology 3 Domain and Guanylate Kinase-Like Domain Required for Channel Clustering by Postsynaptic Density-95/SAP90

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