Sema4b colocalizes with psd95 at synaptic contacts between cultured hippocampal neurons. Abstract background the authors have shown previously that inhaled anesthetics disrupt the interaction between the second postsynaptic density protein95, drosophila disc large tumor suppressor, and zonula occludens1 pdz domain of postsynaptic density protein95 psd95 and the cterminus of nmethyldaspartate receptor subunits nr2a and nr2b. Cellularmolecular regulationofdendriticspines,spatialmemory,and embryonicdevelopmentbythetancfamilyof psd 95 interactingproteins seungnamhan,1jungyongnam,1yanli,1. Jan 08, 2014 aberrant synaptic dysfunction is implicated in the pathogenesis of schizophrenia. Constitutively active kir2 channels as well as g proteingated kir3. Psd95sap90 family members have been found in both postsynaptic and presynaptic regions. The psd 95 sap90 family of scaffold proteins organizes the postsynaptic density psd and regulates nmda receptor signaling at excitatory synapses. Using structural biology, cell biology, and electrophysiology approaches, zhu et al. Nterminal palmitoylation of psd95 is necessary for its synaptic localization, clustering of receptors 33. Nedlgsap102 and nr2b colocalize at synaptic sites in cultured rat hippocampal neurons, and their expressions increase in parallel with the onset of. Aberrant synaptic dysfunction is implicated in the pathogenesis of schizophrenia. Docs integration, interface with chrome apps and drive android all add to the charm.
Inhalational anesthetics disrupt postsynaptic density protein. Psd 95 contains one sh3 domain in its carboxyterminal domain, as well as three conserved repeat regions called glgf or pdz domains. Psd95 controls the number of ampars at the psd through interactions with auxiliary proteins. Neurexinneuroligin adhesions capture surfacediffusing. Using a yeast twohybrid screen and gst pulldown assays we show that sapap3 sap90 psd95associated protein3 interacts with fak residues 676840 and pyk2. Postsynaptic density assembly is fundamentally different. Strikingly, when all of the data were plotted together and combined with similar data concerning the recruitment kinetics of sap90psd95 bresler et al. If you have pending orders, we will email you to confirm that your organization can accept shipments prior to shipping your order.
Post synaptic density 95 kda psd 95, also known as synapse associated protein 90 kda sap90, is one of a family of membraneassociated proteins found in the postsynaptic density in forebrain neurons and certain presynaptic structures in the cerebellum. The three proteins partly codistribute in the same sucrose gradient fractions as the postsynaptic density protein psd95 and src. Ultrastructural analyses of psd95transfected pyramidal neurons. A big advantage is drives ability to recognise and open more than 30 file types, including hd video files and adobe illustrator and psd files. Sh3 domains in general are intriguing targets for studying signal transduction process, drug design and protein folding dynamics. Psd file definition of psd file by medical dictionary. Gkap orchestrates activitydependent postsynaptic protein. Effect of psd 95 sap90 andor psd 93chapsyn110 deficiency on the minimum alveolar anesthetic concentration of halothane in mice you will receive an email whenever this article is corrected, updated, or cited in the literature. Sap90psd95 is thought to be a central organizer of the glutamatergic synapse postsynaptic reception apparatus. Post synaptic density 95 kda psd95, also known as synapse associated protein 90 kda sap90, is one of a family of membraneassociated proteins found. Psd95 sap90 is a protein that interacts with the nmda receptor nmdar2b, neuronal nos nnos or bnos, and other proteins. Semaphorin 4b interacts with the postsynaptic density. Psd95 contains one sh3 domain in its carboxyterminal domain, as well as three conserved repeat regions called glgf or pdz domains. Tested in western blot wb, immunofluorescence if, immunocytochemistry icc, immunoprecipitation ip and elisa elisa applications.
Cells were grown in low potassium to favour functional synapse formation in vitro. Hindiii and ecori were used to cut psd95 from psd95pgw1 received from david bredt and ligate it into ptagrfpn. Coexpression of sema4b with psd 95 in cos 7 cells results in the clustering of sema4b. To evaluate the role of kif5, conventional kinesin, in the dendritic transport of psd 95 protein, we. To assess its potential role during glutamatergic synapse formation, we used gfp. Journal of neuroscience 21 september 2011, 31 38 500. This sequence mediates the interaction with the post. In excitatory synapses, psd 95 clusters receptors and ion channels at specific sites in the postsynaptic membrane and organizes downstream signaling and cytoskeletal molecules. The dynamics of sap90psd95 recruitment to new synaptic. Various bait constructs containing cdna sequences corresponding to the phosphatase domains andor the cterminal region of ptp. Regulation of dendritic spine morphology by spar, a psd95. Jan 01, 2000 several signaling proteins clustered at the postsynaptic density specialization in neurons harbor a conserved cterminal pdz domain recognition sequence xstxvi that mediates binding to members of the psd 95 sap90 protein family. Psd file article about psd file by the free dictionary.
Psd95 is a member of the membraneassociated guanylate kinase maguk family, the members of which consist of multiple proteinprotein interaction motifs, including one or more copies of a pdz domain, an src homology 3 sh3 domain, a bridging region known as a hook region, and a guanylate kinase gklike domain 14. Effect of psd95sap90 andor psd93chapsyn110 deficiency on the minimum alveolar anesthetic concentration of halothane in mice you will receive an email whenever this article is corrected, updated, or cited in the literature. Structural modeling of protein interactions by analogy. This synaptic localization depends on the presence of the pdzbinding motif. The maguks are defined by their inclusion of pdz, sh3 and guk domains, although many of them also contain regions homologous of camkii, ww and l27 domains. We have resumed shipping of plasmid orders in a reduced capacity. Johannes hells lab contains the insert psd95 and is published in unpublished this plasmid is available through addgene. Signals were quantified through densitometry using photoshop cs3 software adobe. In the cerebellum, psd95sap90 was localized in presynaptic nerve terminals of inhibitory synapses, while in the forebrain, it was found at psd. Psdk is listed in the worlds largest and most authoritative dictionary database of abbreviations and acronyms the free dictionary. Camkiia binds to factin via its interaction with camkiib, psd 95 binds to map1a and cript, both of which are microtubulebinding proteins, and the nr1 subunit of the. Postsynaptic scaffolds of excitatory and inhibitory synapses. Fak and pyk2 interact with sap90psd95associated protein. B the calcium dependence of the interaction between psd95 and calmodulin was determined.
Coexpression of sema4b with psd95 in cos 7 cells results in the clustering of sema4b. Immunofluorescent staining using a psd95 antibody was performed on a half of the mouse brain after clarifying it using the advanced cubic protocol. Cellularmolecular regulationofdendriticspines,spatialmemory. It is noteworthy that the binding of nedlgsap102 and psd 95 sap90 is not mediated by their pdz domains. Here, we ask whether the synaptic scaffolding protein psd95 postsynaptic density 95 participates in ampar incorporation during two forms of synaptic plasticity. They also developed a potent nonphosphorylated psd95 gk inhibitory peptide that can effectively disrupt the sapappsd. Post synaptic density 95 kda psd95, also known as synapse associated protein 90 kda sap90, is one of a family of membraneassociated proteins found in the postsynaptic density in forebrain neurons and certain presynaptic structures in the cerebellum. We examined here the ability of neurexinneuroligin adhesions to mobilize ampatype glutamate receptors ampars at postsynapses through a diffusiontrap process involving the scaffold molecule psd 95.
However, its contribution to synapse formation and organization remains unclear. Effect of psd95sap90 andor psd93chapsyn110 deficiency. Looking for online definition of psdk or what psdk stands for. A family of psd95sap90associated proteins localized at. Psd 95 is believed to participate in the clustering of certain proteins, including nmda receptors, shakertype potassium channels at the synaptic membrane in central nervous system cns neurons.
Linial m 1995 nucleotide binding by the synapse associated protein sap90. Psd95sap90binding protein 3, sap90psd 95 associated protein 3, sapap3 feature type. Nedlgsap102, a neuronal and endocrine tissuespecific membraneassociated guanylate kinase family protein, is known to bind to cterminal ends ofnmethyldaspartate receptor 2b nr2b through its pdz psd95dlgzo1 domains. The lollipop plot above illustrates recurrent observed in 3 or more out of 4440 tcga tumor samples from 15 cancer types and therefore potentially oncogenic missense mutations click on show cancer mutations. Dlg associated protein 2 synonyms 6430596n04rik, dap2, psd95sap90binding protein 2, sap90psd95associated protein 2, sapap2. Psd synonyms, psd pronunciation, psd translation, english dictionary definition of psd. This synaptic localization depends on the presence of. Sema4b colocalizes with psd 95 at synaptic contacts between cultured hippocampal neurons. To overcome the problem of fusion tag removal, we cloned both sh3hookguk domains sap90psd95 and sap97 in a pet21a expression vector without tag and overexpressed the constructs in e. The dlgap2 gene encoding the sap90psd 95associated protein 2 sapap2 located at the postsynaptic density of neuronal cells is involved in the neuronal synaptic function.
Sap90psd95 was expressed as a soluble protein, when induced at 37 c with 0. The layers enable an illustration to be created from individual graphic elements that can be moved around repeatedly, one on top of the other, until the desired result is obtained. This study aimed to investigate whether the dlgap2 gene is associated with schizophrenia. Addgene continues to monitor the changing covid19 situation. Begain brainenriched guanylate kinaseassociated protein. Although the transport and regulation of psd95 in synaptic regions is well understood, dendritic transport of psd95 before synaptic localization still remains to be clarified. Inhalational anesthetics disrupt postsynaptic density.
Looking for online definition of psd or what psd stands for. Psd 95 sap90 binds various proteins through the pdz domains and organizes synaptic junctions. Psd95sap90binding protein 2, sap90psd95associated protein 2, sapap2 feature type. Postsynaptic density protein 95, disks large homolog 4, synapseassociated protein 90, sap90. Like all magukfamily proteins, its basic structure includes three pdz domains, an sh3 domain, and a guanylate kinaselike domain gk connected by disordered linker regions. Immunofluorescent staining using a psd 95 antibody was performed on a half of the mouse brain after clarifying it using the advanced cubic protocol. In hippocampal slice cultures, the expression of psd95green fluorescent protein. To examine the effect of psd95 overexpression on spine morphology, we transfected hippocampal organotypic slice cultures with a psd95 tagged with egfp using a biolistic approach. Psd95sap90 binds various proteins through the pdz domains and organizes synaptic junctions. Using a combined electron microscopic, genetic, and pharmacological approach, we uncover a new mechanism through which psd95 regulates synaptogenesis. Psd95 antibodies post synaptic density 95 kda psd95, also known as synapse associated protein 90 kda sap90, is one of a family of membraneassociated proteins found in the postsynaptic density in forebrain neurons and certain presynaptic structures in the cerebellum. Psd95 encoded by dlg4 is a member of the maguk superfamily, and part of a subfamily which also includes psd93, sap97 and sap102. There are two principal modes of interaction between psd 95 and other proteins. A family of psd95sap90associated proteins localized at postsynaptic density.
Interaction of nedlgsap102, a neuronal and endocrine tissue. Role of the dlgap2 gene encoding the sap90psd95associated. Psd95 serves as a major scaffold for other signaling proteins. Members of the postsynaptic density95 psd95sap90 family of membraneassociated guanylate kinase maguk proteins function as multimodular scaffolds that organize proteinsignaling complexes at neuronal synapses. This antibody reacts with human, mouse, rat samples. Postsynaptic density protein 95 psd95 is transported by. Sep 21, 2011 the mechanisms governing the recruitment of functional glutamate receptors at nascent excitatory postsynapses following initial axondendrite contact remain unclear. Dap3, prpl8, psd95sap90binding protein 3, sap90psd 95 associated protein 3, sapap3. Sapap3 psd95sap90binding protein 3, also known as dlgap3 disks largeassociated protein 3 or dap3, is a 979 amino acid protein that belongs to the sapap family of psd95.
Psd 95 sap90 is a protein that interacts with the nmda receptor nmdar2b, neuronal nos nnos or bnos, and other proteins. Interaction of nedlgsap102, a neuronal and endocrine. Although the transport and regulation of psd 95 in synaptic regions is well understood, dendritic transport of psd 95 before synaptic localization still remains to be clarified. Its all coming together with the psd95sap90 protein family. Dec 15, 2015 psd95 and psd93 include nterminal palmitoylation sites that enable psd95 and psd93 to associate with membrane lipids. Psd95sap90 is a synaptic membraneassociated guanylate kinase with three pdz, one sh3, and one guanylate kinase gk domain. The making of drawings in accordance with the rules of mathematics, as in engineering or architecture. The dlgap2 gene encoding the sap90 psd 95 associated protein 2 sapap2 located at the postsynaptic density of neuronal cells is involved in the neuronal synaptic function. The dlgap2 gene encoding the sap90psd95associated protein 2 sapap2 located at the postsynaptic density of neuronal cells is involved in the neuronal synaptic function. Some of the proteins associated with the psd are fodrin, tubulin, calmodulin, cam kinase ii, psd95, and psd93. The present study aims to show psd95 distribution in 3 dimensions 3d without slicing the brain tissue of c57bl6 mice into sections using the advanced cubic technique.
Takeuchi m1, hata y, hirao k, toyoda a, irie m, takai y. Interaction between fulllength psd95 and calmodulin. To evaluate the role of kif5, conventional kinesin, in the dendritic transport of psd95 protein, we. Several signaling proteins clustered at the postsynaptic density specialization in neurons harbor a conserved cterminal pdz domain recognition sequence xstxvi that mediates binding to members of the psd95sap90 protein family. Embo press is an editorially independent publishing platform for the development of embo scientific publications. Psd95 family maguks are essential for anchoring ampa and. The regulated delivery of ampatype glutamate receptors ampars to synapses is an important mechanism underlying synaptic plasticity. Jun 16, 2005 this sequence mediates the interaction with the post. Psd is listed in the worlds largest and most authoritative dictionary database of abbreviations and acronyms the free dictionary. Analysis of a series of psd95 mutants revealed that distinct domains stabilize psd95 within the psd and contribute to psd formation. The dlgap2 gene encoding the sap90psd95associated protein 2. We find that psd95 is highly stable within the spine, more so than other psdassociated proteins such as camkii. Johannes hells lab contains the insert psd 95 and is published in unpublished this plasmid is available through addgene.
Read developmental regulation of psd95 and nnos expression in lumbar spinal cord of rats, neurochemistry international on deepdyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips. We report that spar, a rapspecific gtpaseactivating protein rapgap, interacts with the guanylate kinaselike domain of psd95 and forms a complex with psd95 and nmda receptors in brain. The psd95sap90 family of scaffold proteins organizes the postsynaptic density psd and regulates nmda receptor signaling at excitatory synapses. We report that spar, a rapspecific gtpaseactivating protein rapgap, interacts with the guanylate kinaselike domain of psd 95 and forms a complex with psd 95 and nmda receptors in brain.
Postsynaptic scaffolds of excitatory and inhibitory. Nov 21, 2019 postsynaptic density protein 95 psd 95 is a pivotal postsynaptic scaffolding protein in excitatory neurons. Psd95 promotes synaptogenesis and multiinnervated spine. Dec 15, 2008 ultrastructural analyses of psd95transfected pyramidal neurons. Postsynaptic density protein 95 psd95 is a pivotal postsynaptic scaffolding protein in excitatory neurons. Nov 11, 2012 gkap refers to a family of four scaffold proteins initially identified by their interaction with the guanylate kinase domain of psd95 hence named guanylate kinaseassociated protein or sap90. Postsynaptic density 95 psd95 is an important regulator of synaptic structure and plasticity.
Postsynaptic density 95 kda protein psd95 is an important molecule on the. Camkiia binds to factin via its interaction with camkiib, psd95 binds to map1a and cript, both of which are microtubulebinding proteins, and the nr1 subunit of the. Psd 95 encoded by dlg4 is a member of the maguk superfamily, and part of a subfamily which also includes psd 93, sap97 and sap102. Sap97hdlg was localized at presynaptic terminals in the forebrain. Gkap refers to a family of four scaffold proteins initially identified by their interaction with the guanylate kinase domain of psd95 hence named guanylate kinaseassociated protein or sap90. Neurexinneuroligin adhesions capture surfacediffusing ampa receptors through psd95 scaffolds.
Psd95 or sap90 is the best studied member of the magukfamily of pdz domaincontaining proteins. Neurexinneuroligin adhesions capture surfacediffusing ampa. Some of the proteins associated with the psd are fodrin, tubulin, calmodulin, cam kinase ii, psd 95, and psd 93. Longterm depression was induced in 45weekold hippocampal slices with 900 pairedpulse stimulation delivered at 1 hz. Psd95sap90 and psd93chapsyn110 have been identified to attach nmda receptors to the internal signaling molecules at neuronal synapses. Sep 12, 2018 the present study aims to show psd 95 distribution in 3 dimensions 3d without slicing the brain tissue of c57bl6 mice into sections using the advanced cubic technique. Analysis of the amino acid sequence of sh3hookguk region of sap90psd95 and sap97 reveals that both are quite similar, except that there is an insertion of 37 i2 motif or 33 amino acid residues i3 motif in sap97 fig. In excitatory synapses, psd95 clusters receptors and ion channels at specific sites in the postsynaptic membrane and organizes downstream signaling and cytoskeletal molecules.
67 1072 415 12 282 1224 811 151 894 318 593 1138 1179 1496 1191 337 1222 1308 22 1485 309 762 66 996 1121 1190 896 1386 1221