Nuclear speckles and nucleoli targeting by PIP2-PDZ domain interactions.

Abstract

PDZ (Postsynaptic density protein, Disc large, Zona occludens) domains are protein-protein interaction modules that predominate in submembranous scaffolding proteins. Recently, we showed that the PDZ domains of syntenin-1 also interact with phosphatidylinositol 4,5-bisphosphate (PIP2) and that this interaction controls the recruitment of the protein to the plasma membrane. Here we evaluate the general importance of PIP2-PDZ domain interactions. We report that most PDZ proteins bind weakly to PIP2, but that syntenin-2, the closest homolog of syntenin-1, binds with high affinity to PIP2 via its PDZ domains. Surprisingly, these domains target syntenin-2 to nuclear PIP2 pools, in nuclear speckles and nucleoli. Targeting to these sites is abolished by treatments known to affect these PIP2 pools. Mutational and domain-swapping experiments indicate that high-affinity binding to PIP2 requires both PDZ domains of syntenin-2, but that its first PDZ domain contains the nuclear PIP2 targeting determinants. Depletion of syntenin-2 disrupts the nuclear speckles-PIP2 pattern and affects cell survival and cell division. These findings show that PIP2-PDZ domain interactions can directly contribute to subnuclear assembly processes.

• Authors: Eva Mortier, Gunther Wuytens, Iris Leenaerts, Femke Hannes, Man Y Heung, Gisèle Degeest, Guido David, Pascale Zimmermann
• Journal: The EMBO journal (EMBO J) Vol. 24 Issue 14 Pg. 2556-65 (Jul 20 2005) ISSN: 0261-4189 [Print] England
• PMID: 15961997 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carrier Proteins
• Intracellular Signaling Peptides and Proteins
• Lipid Bilayers
• Membrane Proteins
• Nerve Tissue Proteins
• Phosphatidylinositol 4,5-Diphosphate
• SDCBP protein, human
• SDCBP2 protein, human
• Syntenins
• postsynaptic density proteins

Topics

• Carrier Proteins (metabolism)
• Cell Division (physiology)
• Cell Line, Tumor
• Cell Membrane (metabolism)
• Cell Nucleolus (metabolism)
• Cell Nucleus (metabolism)
• Cell Survival (physiology)
• Cells, Cultured
• Humans
• Intracellular Signaling Peptides and Proteins (metabolism)
• Lipid Bilayers (metabolism)
• Membrane Proteins (metabolism)
• Nerve Tissue Proteins (metabolism)
• Phosphatidylinositol 4,5-Diphosphate (metabolism)
• Protein Interaction Mapping
• Protein Structure, Tertiary
• Syntenins
• Time Factors