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https://www.readbyqxmd.com/read/29703139/identification-of-a-novel-dlg2-isoform-differentially-expressed-in-ifn%C3%AE-producing-plasmacytoid-dendritic-cells
#1
Shafaqat Ali, Alexander Hoven, Regine J Dress, Heiner Schaal, Judith Alferink, Stefanie Scheu
BACKGROUND: The murine discs large homolog 2 (DLG2; post synaptic density 93 (PSD-93); Chapsyn-110) is a member of the membrane-associated guanylate kinase (MAGUK) protein family involved in receptor assembly and associated with signaling enzymes on cell membranes. In neurons, DLG2 protein isoforms derived from alternatively spliced transcripts have been described to bind to NMDA (N-methyl-aspartate) receptors and K channels and to mediate clustering of these channels in the postsynaptic membrane...
March 12, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29625175/magi-proteins-can-differentially-regulate-the-signaling-pathways-of-5-ht-2a-r-by-enhancing-receptor-trafficking-and-plc-recruitment
#2
Maha M Hammad, Henry A Dunn, Stephen S G Ferguson
MAGI proteins are Membrane-Associated Guanylate Kinase Inverted proteins that belong to the MAGUK family. They are scaffolding proteins that were shown to mediate the trafficking and signaling of various G protein-coupled receptors (GPCRs). They contain PDZ domains in their structure and most GPCRs interact with these proteins via the PDZ motifs on the carboxyl terminal end of a receptor. In a PDZ overlay assay performed with the carboxyl terminal tail of 5-HT2A R, we were able to detect all three members of the MAGI subfamily, MAGI-1, MAGI-2 and MAGI-3 as interacting PDZ proteins...
April 3, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29574717/dynamic-sap102-expression-in-the-hippocampal-subregions-of-rats-and-app-ps1-mice-of-various-ages
#3
Dongning Su, Hui Liu, Tianrong Liu, Xin Zhang, Wei Yang, Yizhi Song, Jinping Liu, Yan Wu, Lirong Chang
The hippocampus is a structurally and functionally complex brain area that plays important and diverse roles in higher brain functions, such as learning and memory, and mounting evidence indicates that different hippocampal subregions play distinctive roles. The hippocampus is also one of the first regions in the brain to suffer damage in Alzheimer's disease (AD). Synaptic dysfunction in the hippocampus, rather than neuronal loss per se, is paralleled by behavioural and functional deficits in AD. The membrane-associated guanylate kinase (MAGUK) family of proteins, including SAP102, PSD-95, PSD-93 and SAP97, have long been recognized as essential components of the postsynaptic density (PSD) at excitatory synapses...
March 25, 2018: Journal of Anatomy
https://www.readbyqxmd.com/read/29382759/assembly-mechanism-of-the-carma1-bcl10-malt1-traf6-signalosome
#4
Liron David, Yang Li, Jun Ma, Ethan Garner, Xinzheng Zhang, Hao Wu
The CARMA1-BCL10-MALT1 (CBM) signalosome is a central mediator of T cell receptor and B cell receptor-induced NF-κB signaling that regulates multiple lymphocyte functions. While caspase-recruitment domain (CARD) membrane-associated guanylate kinase (MAGUK) protein 1 (CARMA1) nucleates B cell lymphoma 10 (BCL10) filament formation through interactions between CARDs, mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is a paracaspase with structural similarity to caspases, which recruits TNF receptor-associated factor 6 (TRAF6) for K63-linked polyubiquitination...
February 13, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29351990/saa3-is-a-key-mediator-of-the-protumorigenic-properties-of-cancer-associated-fibroblasts-in-pancreatic-tumors
#5
Magdolna Djurec, Osvaldo Graña, Albert Lee, Kevin Troulé, Elisa Espinet, Lavinia Cabras, Carolina Navas, María Teresa Blasco, Laura Martín-Díaz, Miranda Burdiel, Jing Li, Zhaoqi Liu, Mireia Vallespinós, Francisco Sanchez-Bueno, Martin R Sprick, Andreas Trumpp, Bruno Sainz, Fátima Al-Shahrour, Raul Rabadan, Carmen Guerra, Mariano Barbacid
Pancreatic ductal adenocarcinoma (PDAC) is characterized by the presence of abundant desmoplastic stroma primarily composed of cancer-associated fibroblasts (CAFs). It is generally accepted that CAFs stimulate tumor progression and might be implicated in drug resistance and immunosuppression. Here, we have compared the transcriptional profile of PDGFRα+ CAFs isolated from genetically engineered mouse PDAC tumors with that of normal pancreatic fibroblasts to identify genes potentially implicated in their protumorigenic properties...
February 6, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29281827/synaptic-targeting-and-function-of-sapaps-mediated-by-phosphorylation-dependent-binding-to-psd-95-maguks
#6
Jinwei Zhu, Qingqing Zhou, Yuan Shang, Hao Li, Mengjuan Peng, Xiao Ke, Zhuangfeng Weng, Rongguang Zhang, Xuhui Huang, Shawn S C Li, Guoping Feng, Youming Lu, Mingjie Zhang
The PSD-95/SAPAP/Shank complex functions as the major scaffold in orchestrating the formation and plasticity of the post-synaptic densities (PSDs). We previously demonstrated that the exquisitely specific SAPAP/Shank interaction is critical for Shank synaptic targeting and Shank-mediated synaptogenesis. Here, we show that the PSD-95/SAPAP interaction, SAPAP synaptic targeting, and SAPAP-mediated synaptogenesis require phosphorylation of the N-terminal repeat sequences of SAPAPs. The atomic structure of the PSD-95 guanylate kinase (GK) in complex with a phosphor-SAPAP repeat peptide, together with biochemical studies, reveals the molecular mechanism underlying the phosphorylation-dependent PSD-95/SAPAP interaction, and it also provides an explanation of a PSD-95 mutation found in patients with intellectual disabilities...
December 26, 2017: Cell Reports
https://www.readbyqxmd.com/read/29261291/structures-of-the-l27-domain-of-disc-large-homologue-1-protein-illustrate-a-self-assembly-module
#7
Agnidipta Ghosh, Udupi A Ramagopal, Jeffrey B Bonanno, Michael Brenowitz, Steven C Almo
Disc large 1 (Dlg1) proteins, members of the MAGUK protein family, are linked to cell polarity via their participation in multiprotein assemblies. At their N-termini, Dlg1 proteins contain a L27 domain. Typically, the L27 domains participate in the formation of obligate hetero-oligomers with the L27 domains from their cognate partners. Among the MAGUKs, Dlg1 proteins exist as homo-oligomers, and the oligomerization is solely dependent on the L27 domain. Here we provide biochemical and structural evidence of homodimerization via the L27 domain of Dlg1 from Drosophila melanogaster...
February 27, 2018: Biochemistry
https://www.readbyqxmd.com/read/29250591/shank-proteins-differentially-regulate-synaptic-transmission
#8
Rebecca Shi, Patrick Redman, Dipanwita Ghose, Yan Liu, Xiaobai Ren, Lei J Ding, Mingna Liu, Kendrick J Jones, Weifeng Xu
Shank proteins, one of the principal scaffolds in the postsynaptic density (PSD) of the glutamatergic synapses, have been associated with autism spectrum disorders and neuropsychiatric diseases. However, it is not known whether different Shank family proteins have distinct functions in regulating synaptic transmission, and how they differ from other scaffold proteins in this aspect. Here, we investigate the role of Shanks in regulating glutamatergic synaptic transmission at rat hippocampal SC-CA1 synapses, using lentivirus-mediated knockdown and molecular replacement combined with dual whole-cell patch clamp in hippocampal slice culture...
November 2017: ENeuro
https://www.readbyqxmd.com/read/29194363/the-e3-ubiquitin-ligase-rnf7-negatively-regulates-card14-carma2sh-signaling
#9
Gianluca Telesio, Ivan Scudiero, Maddalena Pizzulo, Pellegrino Mazzone, Tiziana Zotti, Serena Voccola, Immacolata Polvere, Pasquale Vito, Romania Stilo
The three CARD-containing MAGUK (CARMA) proteins function as scaffolding molecules that regulate activation of the pro-inflammatory transcription factor NF-κB. Recently, mutations in CARMA2 have been linked to psoriasis susceptibility due to their acquired altered capacity to activate NF-κB. By means of two-hybrid screening with yeast, we identified RING finger protein 7 (RNF7) as an interactor of CARMA2. We present evidence that RNF7 functions as a negative regulator of the NF-κB-activating capacity of CARMA2...
December 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29138001/pdz-ligand-binding-induced-conformational-coupling-of-the-pdz-sh3-gk-tandems-in-psd-95-family-maguks
#10
Menglong Zeng, Fei Ye, Jia Xu, Mingjie Zhang
Discs large (DLG) MAGUKs are abundantly expressed in glutamatergic synapses, crucial for synaptic transmission, and plasticity by anchoring various postsynaptic components including glutamate receptors, downstream scaffold proteins and signaling enzymes. Different DLG members have shared structures and functions, but also contain unique features. How DLG family proteins function individually and cooperatively is largely unknown. Here, we report that PSD-95 PDZ3 directly couples with SH3-GK tandem in a PDZ ligand binding-dependent manner, and the coupling can promote PSD-95 dimerization and multimerization...
January 5, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28917202/mechanisms-of-maguk-mediated-cellular-junctional-complex-organization
#11
REVIEW
Fei Ye, Menglong Zeng, Mingjie Zhang
Membrane-associated guanylate kinases (MAGUKs) are a family of scaffold proteins that are enriched in cellular junctions and essential for tissue development and homeostasis. Mutations of MAGUKs are linked to many human diseases including cancers, psychiatric disorders, and intellectual disabilities. MAGUKs share a common PDZ-SH3-GK tandem domain organization at the C-terminal end. In this review, we summarize the mechanistic basis governing target recognition and regulations of this binding by the PDZ-SH3-GK tandem of various MAGUKs...
February 2018: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/28894005/varicose-and-cheerio-collaborate-with-pebble-to-mediate-semaphorin-1a-reverse-signaling-in-drosophila
#12
Sangyun Jeong, Da-Som Yang, Young Gi Hong, Sarah P Mitchell, Matthew P Brown, Alex L Kolodkin
The transmembrane semaphorin Sema-1a acts as both a ligand and a receptor to regulate axon-axon repulsion during neural development. Pebble (Pbl), a Rho guanine nucleotide exchange factor, mediates Sema-1a reverse signaling through association with the N-terminal region of the Sema-1a intracellular domain (ICD), resulting in cytoskeletal reorganization. Here, we uncover two additional Sema-1a interacting proteins, varicose (Vari) and cheerio (Cher), each with neuronal functions required for motor axon pathfinding...
September 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28701415/structure-of-the-psd-95-map1a-complex-reveals-a-unique-target-recognition-mode-of-the-maguk-gk-domain
#13
Yitian Xia, Yuan Shang, Rongguang Zhang, Jinwei Zhu
The PSD-95 family of membrane-associated guanylate kinases (MAGUKs) are major synaptic scaffold proteins and play crucial roles in the dynamic regulation of dendritic remodelling, which is understood to be the foundation of synaptogenesis and synaptic plasticity. The guanylate kinase (GK) domain of MAGUK family proteins functions as a phosphor-peptide binding module. However, the GK domain of PSD-95 has been found to directly bind to a peptide sequence within the C-terminal region of neuronal-specific microtubule-associated protein 1A (MAP1A), although the detailed molecular mechanism governing this phosphorylation-independent interaction at the atomic level is missing...
August 10, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28577431/supramolecular-organization-of-nmda-receptors-and-the-postsynaptic-density
#14
REVIEW
René Aw Frank, Seth Gn Grant
The postsynaptic density (PSD) of all vertebrate species share a highly complex proteome with ∼1000 conserved proteins that function as sophisticated molecular computational devices. Here, we review recent studies showing that this complexity can be understood in terms of the supramolecular organization of proteins, which self-assemble within a hierarchy of different length scales, including complexes, supercomplexes and nanodomains. We highlight how genetic and biochemical approaches in mice are being used to uncover the native molecular architecture of the synapse, revealing hitherto unknown molecular structures, including highly selective mechanisms for specifying the assembly of NMDAR-MAGUK supercomplexes...
August 2017: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/28533267/the-kv1-associated-molecules-tag-1-and-caspr2-are-selectively-targeted-to-the-axon-initial-segment-in-hippocampal-neurons
#15
Delphine Pinatel, Bruno Hivert, Margaux Saint-Martin, Nelly Noraz, Maria Savvaki, Domna Karagogeos, Catherine Faivre-Sarrailh
Caspr2 and TAG-1 (also known as CNTNAP2 and CNTN2, respectively) are cell adhesion molecules (CAMs) associated with the voltage-gated potassium channels Kv1.1 and Kv1.2 (also known as KCNA1 and KCNA2, respectively) at regions controlling axonal excitability, namely, the axon initial segment (AIS) and juxtaparanodes of myelinated axons. The distribution of Kv1 at juxtaparanodes requires axo-glial contacts mediated by Caspr2 and TAG-1. In the present study, we found that TAG-1 strongly colocalizes with Kv1.2 at the AIS of cultured hippocampal neurons, whereas Caspr2 is uniformly expressed along the axolemma...
July 1, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28436082/tricellulin-is-a-target-of-the-ubiquitin-ligase-itch
#16
Susanne Jennek, Sonnhild Mittag, Juliane Reiche, Julie K Westphal, Stefanie Seelk, Max J Dörfel, Thorsten Pfirrmann, Karlheinz Friedrich, Anja Schütz, Udo Heinemann, Otmar Huber
Tricellulin, a member of the tight junction-associated MAGUK protein family, preferentially localizes to tricellular junctions in confluent polarized epithelial cell layers and is downregulated during the epithelial-mesenchymal transition. Posttranslational modifications are assumed to play critical roles in the process of downregulation of tricellulin at the protein level. Here, we report that the E3 ubiquitin ligase Itch forms a complex with tricellulin and thereby enhances its ubiquitination. Pull-down assays confirmed a direct interaction between tricellulin and Itch, which is mediated by the Itch WW domain and the N-terminus of tricellulin...
June 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28388013/protracted-and-asynchronous-accumulation-of-psd95-family-maguks-during-maturation-of-nascent-dendritic-spines
#17
Jason T Lambert, Travis C Hill, Deborah K Park, Julie H Culp, Karen Zito
The formation and stabilization of new dendritic spines is a key component of the experience-dependent neural circuit plasticity that supports learning, but the molecular maturation of nascent spines remains largely unexplored. The PSD95-family of membrane-associated guanylate kinases (PSD-MAGUKs), most notably PSD95, has a demonstrated role in promoting spine stability. However, nascent spines contain low levels of PSD95, suggesting that other members of the PSD-MAGUK family might act to stabilize nascent spines in the early stages of spiny synapse formation...
October 2017: Developmental Neurobiology
https://www.readbyqxmd.com/read/28283559/a-rare-variant-identified-within-the-glun2b-c-terminus-in-a-patient-with-autism-affects-nmda-receptor-surface-expression-and-spine-density
#18
Shuxi Liu, Liang Zhou, Hongjie Yuan, Marta Vieira, Antonio Sanz-Clemente, John D Badger, Wei Lu, Stephen F Traynelis, Katherine W Roche
NMDA receptors (NMDARs) are ionotropic glutamate receptors that are crucial for neuronal development and higher cognitive processes. NMDAR dysfunction is involved in a variety of neurological and psychiatric diseases; however, the mechanistic link between the human pathology and NMDAR dysfunction is poorly understood. Rare missense variants within NMDAR subunits have been identified in numerous patients with mental or neurological disorders. We specifically focused on the GluN2B NMDAR subunit, which is highly expressed in the hippocampus and cortex throughout development...
April 12, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28236779/maguks-multifaceted-synaptic-organizers
#19
REVIEW
Sehoon Won, Jon M Levy, Roger A Nicoll, Katherine W Roche
The PSD-95 family of proteins, known as MAGUKs, have long been recognized to be central building blocks of the PSD. They are categorized as scaffolding proteins, which link surface-expressed receptors to the intracellular signaling molecules. Although the four members of the PSD-95 family (PSD-95, PSD-93, SAP102, and SAP97) have many shared roles in regulating synaptic function, recent studies have begun to delineate specific binding partners and roles in plasticity. In the current review, we will highlight the conserved and unique roles of these proteins...
April 2017: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/28186199/ubiquitination-mediates-kv1-3-endocytosis-as-a-mechanism-for-protein-kinase-c-dependent-modulation
#20
Ramón Martínez-Mármol, Katarzyna Styrczewska, Mireia Pérez-Verdaguer, Albert Vallejo-Gracia, Núria Comes, Alexander Sorkin, Antonio Felipe
The voltage-dependent potassium channel Kv1.3 plays essential physiological functions in the immune system. Kv1.3, regulating the membrane potential, facilitates downstream Ca(2+) -dependent pathways and becomes concentrated in specific membrane microdomains that serve as signaling platforms. Increased and/or delocalized expression of the channel is observed at the onset of several autoimmune diseases. In this work, we show that adenosine (ADO), which is a potent endogenous modulator, stimulates PKC, thereby causing immunosuppression...
February 10, 2017: Scientific Reports
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