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https://www.readbyqxmd.com/read/28917202/mechanisms-of-maguk-mediated-cellular-junctional-complex-organization
#1
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...
September 13, 2017: 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
#2
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 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28701415/structure-of-psd-95-map1a-complex-reveals-unique-target-recognition-mode-of-maguk-gk-domain
#3
Yitan 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 remodeling 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), though the detailed molecular mechanism governing this phosphorylation-independent interaction at the atomic level is missing...
July 12, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28577431/supramolecular-organization-of-nmda-receptors-and-the-postsynaptic-density
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/28087714/dlg5-connects-cell-polarity-and-hippo-signaling-protein-networks-by-linking-par-1-with-mst1-2
#11
Julian Kwan, Anna Sczaniecka, Emad Heidary Arash, Liem Nguyen, Chia-Chun Chen, Srdjana Ratkovic, Olga Klezovitch, Liliana Attisano, Helen McNeill, Andrew Emili, Valeri Vasioukhin
Disruption of apical-basal polarity is implicated in developmental disorders and cancer; however, the mechanisms connecting cell polarity proteins with intracellular signaling pathways are largely unknown. We determined previously that membrane-associated guanylate kinase (MAGUK) protein discs large homolog 5 (DLG5) functions in cell polarity and regulates cellular proliferation and differentiation via undefined mechanisms. We report here that DLG5 functions as an evolutionarily conserved scaffold and negative regulator of Hippo signaling, which controls organ size through the modulation of cell proliferation and differentiation...
December 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/27861918/membrane-associated-guanylate-kinase-dynamics-reveal-regional-and-developmental-specificity-of-synapse-stability
#12
Jonathan M Levy, Roger A Nicoll
KEY POINTS: The membrane-associated guanylate kinase (MAGUK) family of synaptic scaffolding proteins anchor glutamate receptors at CNS synapses. MAGUK removal via RNAi-mediated knockdown in the CA1 hippocampal region in immature animals causes rapid and lasting reductions in glutamatergic transmission. In mature animals, the same manipulation has little acute effect. The hippocampal dentate gyrus, a region with ongoing adult neurogenesis, is sensitive to MAGUK loss in mature animals, behaving like an immature CA1...
March 1, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/27756895/mpp2-is-a-postsynaptic-maguk-scaffold-protein-that-links-syncam1-cell-adhesion-molecules-to-core-components-of-the-postsynaptic-density
#13
Nils Rademacher, Bettina Schmerl, Jennifer A Lardong, Markus C Wahl, Sarah A Shoichet
At neuronal synapses, multiprotein complexes of trans-synaptic adhesion molecules, scaffold proteins and neurotransmitter receptors assemble to essential building blocks required for synapse formation and maintenance. Here we describe a novel role for the membrane-associated guanylate kinase (MAGUK) protein MPP2 (MAGUK p55 subfamily member 2) at synapses of rat central neurons. Through interactions mediated by its C-terminal SH3-GK domain module, MPP2 binds to the abundant postsynaptic scaffold proteins PSD-95 and GKAP and localises to postsynaptic sites in hippocampal neurons...
October 19, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27642159/an-atypical-maguk-gk-target-recognition-mode-revealed-by-the-interaction-between-dlg-and-kif13b
#14
Jinwei Zhu, Yuan Shang, Yitian Xia, Rongguang Zhang, Mingjie Zhang
The membrane-associated guanylate kinase (MAGUK) scaffold proteins share a signature guanylate kinase (GK) domain. Despite their diverse functional roles in cell polarity control and synaptic signaling, the currently known mode of action of MAGUK GK is via its binding to phosphorylated short peptides from target proteins. Here, we discover that the GK domain of DLG MAGUK binds to an unphosphorylated and autonomously folded domain within the stalk region (MAGUK binding stalk [MBS] domain) of a kinesin motor KIF13B with high specificity and affinity...
November 1, 2016: Structure
https://www.readbyqxmd.com/read/27629719/the-arp2-3-complex-is-essential-for-distinct-stages-of-spine-synapse-maturation-including-synapse-unsilencing
#15
Erin F Spence, Daniel J Kanak, Benjamin R Carlson, Scott H Soderling
UNLABELLED: Dendritic filopodia are actin-rich structures that are thought to contribute to early spine synapse formation; however, the actin regulatory proteins important for early synaptogenesis are poorly defined. Using organotypic hippocampal slice cultures and primary neuron hippocampal cultures from Arp2/3 conditional knock-out mice, we analyze the roles of the Arp2/3 complex, an actin regulator that creates branched actin networks, and demonstrate it is essential for distinct stages of both structural and functional maturation of excitatory spine synapses...
September 14, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27606286/tight-junction-disruption-induced-by-type-3-secretion-system-effectors-injected-by-enteropathogenic-and-enterohemorrhagic-escherichia-coli
#16
REVIEW
Paul Ugalde-Silva, Octavio Gonzalez-Lugo, Fernando Navarro-Garcia
The intestinal epithelium consists of a single cell layer, which is a critical selectively permeable barrier to both absorb nutrients and avoid the entry of potentially harmful entities, including microorganisms. Epithelial cells are held together by the apical junctional complexes, consisting of adherens junctions, and tight junctions (TJs), and by underlying desmosomes. TJs lay in the apical domain of epithelial cells and are mainly composed by transmembrane proteins such as occludin, claudins, JAMs, and tricellulin, that are associated with the cytoplasmic plaque formed by proteins from the MAGUK family, such as ZO-1/2/3, connecting TJ to the actin cytoskeleton, and cingulin and paracingulin connecting TJ to the microtubule network...
2016: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/27573697/presynaptic-dlg-regulates-synaptic-function-through-the-localization-of-voltage-activated-ca-2-channels
#17
César Astorga, Ramón A Jorquera, Mauricio Ramírez, Andrés Kohler, Estefanía López, Ricardo Delgado, Alex Córdova, Patricio Olguín, Jimena Sierralta
The DLG-MAGUK subfamily of proteins plays a role on the recycling and clustering of glutamate receptors (GLUR) at the postsynaptic density. discs-large1 (dlg) is the only DLG-MAGUK gene in Drosophila and originates two main products, DLGA and DLGS97 which differ by the presence of an L27 domain. Combining electrophysiology, immunostaining and genetic manipulation at the pre and postsynaptic compartments we study the DLG contribution to the basal synaptic-function at the Drosophila larval neuromuscular junction...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27558197/membrane-associated-guanylate-kinase-scaffolds-organize-a-horizontal-cell-synaptic-complex-restricted-to-invaginating-contacts-with-photoreceptors
#18
Alejandro Vila, Christopher M Whitaker, John O'Brien
Synaptic processes and plasticity of synapses are mediated by large suites of proteins. In most cases, many of these proteins are tethered together by synaptic scaffold proteins. Scaffold proteins have a large number and typically a variety of protein interaction domains that allow many different proteins to be assembled into functional complexes. Because each scaffold protein has a different set of protein interaction domains and a unique set of interacting partners, the presence of synaptic scaffolds can provide insight into the molecular mechanisms that regulate synaptic processes...
March 1, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/27466188/altered-thalamocortical-development-in-the-sap102-knockout-model-of-intellectual-disability
#19
Alex Crocker-Buque, Stephen P Currie, Liliana L Luz, Seth G Grant, Kevin R Duffy, Peter C Kind, Michael I Daw
Genetic mutations known to cause intellectual disabilities (IDs) are concentrated in specific sets of genes including both those encoding synaptic proteins and those expressed during early development. We have characterized the effect of genetic deletion of Dlg3, an ID-related gene encoding the synaptic NMDA-receptor interacting protein synapse-associated protein 102 (SAP102), on development of the mouse somatosensory cortex. SAP102 is the main representative of the PSD-95 family of postsynaptic MAGUK proteins during early development and is proposed to play a role in stabilizing receptors at immature synapses...
September 15, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27364017/lateral-membrane-specific-maguk-cask-down-regulates-nav1-5-channel-in-cardiac-myocytes
#20
Catherine A Eichel, Adeline Beuriot, Morgan Y E Chevalier, Jean-Sébastien Rougier, Florent Louault, Gilles Dilanian, Julien Amour, Alain Coulombe, Hugues Abriel, Stéphane N Hatem, Elise Balse
RATIONALE: Mechanisms underlying membrane protein localization are crucial in the proper function of cardiac myocytes. The main cardiac sodium channel, NaV1.5, carries the sodium current (INa) that provides a rapid depolarizing current during the upstroke of the action potential. Although enriched in the intercalated disc, NaV1.5 is present in different membrane domains in myocytes and interacts with several partners. OBJECTIVE: To test the hypothesis that the MAGUK (membrane-associated guanylate kinase) protein CASK (calcium/calmodulin-dependent serine protein kinase) interacts with and regulates NaV1...
August 5, 2016: Circulation Research
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