The PDZ2 domain of zonula occludens-1 and -2 is a phosphoinositide binding domain
Autor: | Hui Lu, Moe Phyu Tun, Kris Meerschaert, Wonhwa Cho, Ciska Boucherie, Berlinda Vanloo, Ariane De Ganck, Nitin Bhardwaj, Joël Vandekerckhove, Jan Gettemans, Eline Remue, Gisèle Degeest, Pascale Zimmermann |
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Rok vydání: | 2009 |
Předmět: |
Models
Molecular Phosphatidylinositol 4 5-Diphosphate Gene isoform Blotting Western Green Fluorescent Proteins PDZ domain PDZ Domains Biology Phosphatidylinositols Zonula Occludens-2 Protein Article Cell Line Cellular and Molecular Neuroscience chemistry.chemical_compound Phosphatidylinositol Phosphates Cell Line Tumor Cell polarity Zonula Occludens Proteins medicine Animals Humans Phosphatidylinositol Molecular Biology Cell Nucleus Pharmacology Binding Sites Tight junction Cell Membrane Membrane Proteins Cell Biology Surface Plasmon Resonance Phosphoproteins Protein Structure Tertiary Cell biology medicine.anatomical_structure Amino Acid Substitution Microscopy Fluorescence chemistry Mutation Zonula Occludens-1 Protein Molecular Medicine RNA Interference Postsynaptic density Nucleus HeLa Cells Protein Binding |
Zdroj: | Cellular and Molecular Life Sciences. 66:3951-3966 |
ISSN: | 1420-9071 1420-682X |
Popis: | Zonula occludens proteins (ZO) are postsynaptic density protein-95 discs large-zonula occludens (PDZ) domain-containing proteins that play a fundamental role in the assembly of tight junctions and establishment of cell polarity. Here, we show that the second PDZ domain of ZO-1 and ZO-2 binds phosphoinositides (PtdInsP) and we identified critical residues involved in the interaction. Furthermore, peptide and PtdInsP binding of ZO PDZ2 domains are mutually exclusive. Although lipid binding does not seem to be required for plasma membrane localisation of ZO-1, phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P 2) binding to the PDZ2 domain of ZO-2 regulates ZO-2 recruitment to nuclear speckles. Knockdown of ZO-2 expression disrupts speckle morphology, indicating that ZO-2 might play an active role in formation and stabilisation of these subnuclear structures. This study shows for the first time that ZO isoforms bind PtdInsPs and offers an alternative regulatory mechanism for the formation and stabilisation of protein complexes in the nucleus. |
Databáze: | OpenAIRE |
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