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
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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