scholarly journals MAGUK-Controlled Ubiquitination of CARMA1 Modulates Lymphocyte NF-κB Activity

2009 ◽  
Vol 30 (4) ◽  
pp. 922-934 ◽  
Author(s):  
Miguel E. Moreno-García ◽  
Karen Sommer ◽  
Hisaaki Shinohara ◽  
Ashok D. Bandaranayake ◽  
Tomohiro Kurosaki ◽  
...  
Keyword(s):  
Control Mechanism ◽  
Protein Complexes ◽  
Antigen Receptor ◽  
Lymphocyte Activation ◽  
Adaptor Protein ◽  
Family Protein ◽  
Jnk Activation ◽  
Full Activation ◽  
Maguk Proteins ◽  
Important Structure

ABSTRACT The adaptor protein CARMA1 is required for antigen receptor-triggered activation of IKK and JNK in lymphocytes. Once activated, the events that subsequently turn off the CARMA1 signalosome are unknown. In this study, we found that antigen receptor-activated CARMA1 underwent lysine 48 (K48) polyubiquitination and proteasome-dependent degradation. The MAGUK region of CARMA1 was an essential player in this event; the SH3 and GUK domains contained the main ubiquitin acceptor sites, and deletion of a Hook domain (an important structure for maintaining inactive MAGUK proteins) between SH3 and GUK was sufficient to induce constitutive ubiquitination of CARMA1. A similar deletion promoted the ubiquitination of PSD-95 and Dlgh1, suggesting that a conserved mechanism may control the turnover of other MAGUK family protein complexes. Functionally, we demonstrated that elimination of MAGUK ubiquitination sites in CARMA1 resulted in elevated basal and inducible NF-κB and JNK activation as a result of defective K48 ubiquitination and increased persistence of this ubiquitination-deficient CARMA1 protein in activated lymphocytes. The coordination of degradation with the full activation of the CARMA1 molecule likely provides an intrinsic feedback control mechanism to balance lymphocyte activation upon antigenic stimulation.

MAGUK proteins: structure and role in the tight junction

2000 ◽  
Vol 11 (4) ◽  
pp. 315-324 ◽  
Author(s):  
Lorenza González-Mariscal ◽  
Abigail Betanzos ◽  
Antonia Ávila-Flores
Keyword(s):  
Tight Junction ◽  
Maguk Proteins

Distribution of members of the PSD-95 family of MAGUK proteins at the synaptic region of inner and outer hair cells of the guinea pig cochlea

Synapse ◽  
2001 ◽  
Vol 40 (4) ◽  
pp. 258-268 ◽  
Author(s):  
Caroline Davies ◽  
Debora Tingley ◽  
Bechara Kachar ◽  
Robert J. Wenthold ◽  
Ronald S. Petralia
Keyword(s):  
Guinea Pig ◽  
Hair Cells ◽  
Outer Hair Cells ◽  
Guinea Pig Cochlea ◽  
Synaptic Region ◽  
Maguk Proteins

scholarly journals The Maguk protein, Pals1, functions as an adapter, linking mammalian homologues of Crumbs and Discs Lost

2002 ◽  
Vol 157 (1) ◽  
pp. 161-172 ◽  
Author(s):  
Michael H. Roh ◽  
Olga Makarova ◽  
Chia-Jen Liu ◽  
Shin ◽  
Seonok Lee ◽  
...  
Keyword(s):  
Tight Junctions ◽  
Protein Targeting ◽  
Pdz Domain ◽  
Guanylate Kinase ◽  
Src Homology 3 ◽  
Discs Large ◽  
Domain Of Unknown Function ◽  
Src Homology ◽  
Zona Occludens ◽  
Maguk Proteins

Membrane-associated guanylate kinase (Maguk) proteins are scaffold proteins that contain PSD-95–Discs Large–zona occludens-1 (PDZ), Src homology 3, and guanylate kinase domains. A subset of Maguk proteins, such as mLin-2 and protein associated with Lin-7 (Pals)1, also contain two L27 domains: an L27C domain that binds mLin-7 and an L27N domain of unknown function. Here, we demonstrate that the L27N domain targets Pals1 to tight junctions by binding to a PDZ domain protein, Pals1-associated tight junction (PATJ) protein, via a unique Maguk recruitment domain. PATJ is a homologue of Drosophila Discs Lost, a protein that is crucial for epithelial polarity and that exists in a complex with the apical polarity determinant, Crumbs. PATJ and a human Crumbs homologue, CRB1, colocalize with Pals1 to tight junctions, and CRB1 interacts with PATJ albeit indirectly via binding the Pals1 PDZ domain. In agreement, we find that a Drosophila homologue of Pals1 participates in identical interactions with Drosophila Crumbs and Discs Lost. This Drosophila Pals1 homologue has been demonstrated recently to represent Stardust, a crucial polarity gene in Drosophila. Thus, our data identifies a new multiprotein complex that appears to be evolutionarily conserved and likely plays an important role in protein targeting and cell polarity.

scholarly journals On the role of the MAGUK proteins encoded by Drosophila varicose during embryonic and postembryonic development

2008 ◽  
Vol 8 (1) ◽  
pp. 55 ◽  
Author(s):  
André Bachmann ◽  
Margarete Draga ◽  
Ferdi Grawe ◽  
Elisabeth Knust
Keyword(s):  
Postembryonic Development ◽  
Maguk Proteins

scholarly journals Plasma Membrane Ca2+ATPase Isoform 4b Binds to Membrane-associated Guanylate Kinase (MAGUK) Proteins via Their PDZ (PSD-95/Dlg/ZO-1) Domains

1998 ◽  
Vol 273 (3) ◽  
pp. 1591-1595 ◽  
Author(s):  
Eunjoon Kim ◽  
Steven J. DeMarco ◽  
Shirin M. Marfatia ◽  
Athar H. Chishti ◽  
Morgan Sheng ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Guanylate Kinase ◽  
Maguk Proteins

scholarly journals SUMOylation of the MAGUK protein CASK regulates dendritic spinogenesis

2008 ◽  
Vol 182 (1) ◽  
pp. 141-155 ◽  
Author(s):  
Hsu-Wen Chao ◽  
Chen-Jei Hong ◽  
Tzyy-Nan Huang ◽  
Yi-Ling Lin ◽  
Yi-Ping Hsueh
Keyword(s):  
Rna Interference ◽  
Adhesion Molecules ◽  
Hippocampal Neurons ◽  
Time Course ◽  
Pdz Domain ◽  
Spine Density ◽  
Spine Formation ◽  
Protein 4.1 ◽  
Maguk Protein ◽  
Maguk Proteins

Membrane-associated guanylate kinase (MAGUK) proteins interact with several synaptogenesis-triggering adhesion molecules. However, direct evidence for the involvement of MAGUK proteins in synapse formation is lacking. In this study, we investigate the function of calcium/calmodulin-dependent serine protein kinase (CASK), a MAGUK protein, in dendritic spine formation by RNA interference. Knockdown of CASK in cultured hippocampal neurons reduces spine density and shrinks dendritic spines. Our analysis of the time course of RNA interference and CASK overexpression experiments further suggests that CASK stabilizes or maintains spine morphology. Experiments using only the CASK PDZ domain or a mutant lacking the protein 4.1–binding site indicate an involvement of CASK in linking transmembrane adhesion molecules and the actin cytoskeleton. We also find that CASK is SUMOylated. Conjugation of small ubiquitin-like modifier 1 (SUMO1) to CASK reduces the interaction between CASK and protein 4.1. Overexpression of a CASK–SUMO1 fusion construct, which mimicks CASK SUMOylation, impairs spine formation. Our study suggests that CASK contributes to spinogenesis and that this is controlled by SUMOylation.

scholarly journals The Unique-5 and -6 Motifs of ZO-1 Regulate Tight Junction Strand Localization and Scaffolding Properties

2007 ◽  
Vol 18 (3) ◽  
pp. 721-731 ◽  
Author(s):  
Alan S. Fanning ◽  
Brent P. Little ◽  
Christoph Rahner ◽  
Darkhan Utepbergenov ◽  
Zenta Walther ◽  
...  
Keyword(s):  
Tight Junction ◽  
Tight Junctions ◽  
Cultured Cells ◽  
Variable Region ◽  
Binding Studies ◽  
Vitro Binding ◽  
Complex Protein ◽  
Regulatory Functions ◽  
Maguk Proteins

The proper cellular location and sealing of tight junctions is assumed to depend on scaffolding properties of ZO-1, a member of the MAGUK protein family. ZO-1 contains a conserved SH3-GUK module that is separated by a variable region (unique-5), which in other MAGUKs has proven regulatory functions. To identify motifs in ZO-1 critical for its putative scaffolding functions, we focused on the SH3-GUK module including unique-5 (U5) and unique-6 (U6), a motif immediately C-terminal of the GUK domain. In vitro binding studies reveal U5 is sufficient for occludin binding; U6 reduces the affinity of this binding. In cultured cells, U5 is required for targeting ZO-1 to tight junctions and removal of U6 results in ectopically displaced junction strands containing the modified ZO-1, occludin, and claudin on the lateral cell membrane. These results provide evidence that ZO-1 can control the location of tight junction transmembrane proteins and reveals complex protein binding and targeting signals within its SH3-U5-GUK-U6 region. We review these findings in the context of regulated scaffolding functions of other MAGUK proteins.

scholarly journals Lano, a Novel LAP Protein Directly Connected to MAGUK Proteins in Epithelial Cells

2001 ◽  
Vol 276 (34) ◽  
pp. 32051-32055 ◽  
Author(s):  
Hiroko Saito ◽  
Marie-Josée Santoni ◽  
Jean-Pierre Arsanto ◽  
Fanny Jaulin-Bastard ◽  
André Le Bivic ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Maguk Proteins
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