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Nuclear speckles and nucleoli targeting by PIP 2 –PDZ domain interactions
Author(s) -
Mortier Eva,
Wuytens Gunther,
Leenaerts Iris,
Hannes Femke,
Heung Man Y,
Degeest Gisèle,
David Guido,
Zimmermann Pascale
Publication year - 2005
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600722
Subject(s) - pdz domain , biology , microbiology and biotechnology , scaffold protein , postsynaptic density , nls , nucleolus , cell membrane , nuclear pore , cytoplasm , nuclear localization sequence , cell , biochemistry , signal transduction , receptor , postsynaptic potential
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 (PIP 2 ) and that this interaction controls the recruitment of the protein to the plasma membrane. Here we evaluate the general importance of PIP 2 –PDZ domain interactions. We report that most PDZ proteins bind weakly to PIP 2 , but that syntenin‐2, the closest homolog of syntenin‐1, binds with high affinity to PIP 2 via its PDZ domains. Surprisingly, these domains target syntenin‐2 to nuclear PIP 2 pools, in nuclear speckles and nucleoli. Targeting to these sites is abolished by treatments known to affect these PIP 2 pools. Mutational and domain‐swapping experiments indicate that high‐affinity binding to PIP 2 requires both PDZ domains of syntenin‐2, but that its first PDZ domain contains the nuclear PIP 2 targeting determinants. Depletion of syntenin‐2 disrupts the nuclear speckles–PIP 2 pattern and affects cell survival and cell division. These findings show that PIP 2 –PDZ domain interactions can directly contribute to subnuclear assembly processes.