PIP(2)-PDZ domain binding controls the association of syntenin with the plasma membrane.
PDZ proteins organize multiprotein signaling complexes. According to current views, PDZ domains engage in protein-protein interactions. Here we show that the PDZ domains of several proteins bind phosphatidylinositol 4,5-bisphosphate (PIP(2)). High-affinity binding of syntenin to PIP(2)-containing lipid layers requires both PDZ domains of this protein. Competition and mutagenesis experiments reveal that the protein and the PIP(2) binding sites in the PDZ domains overlap. Overlay assays indicate that the two PDZ domains of syntenin cooperate in binding to cognate peptides and PIP(2). Experiments on living cells demonstrate PIP(2)-dependent and peptide-dependent modes of plasma membrane association of the PDZ domains of syntenin. These observations suggest that local changes in phosphoinositide concentration control the association of PDZ proteins with their target receptors at the plasma membrane.
Zimmermann
Pascale
P
Laboratory for Glycobiology and Developmental Genetics, Department of Human Genetics, University of Leuven, B-3000 Leuven, Belgium. pascale.zimmermann@med.kuleuven.ac.be
Meerschaert
Kris
K
Reekmans
Gunter
G
Leenaerts
Iris
I
Small
J Victor
JV
Vandekerckhove
Joël
J
David
Guido
G
Gettemans
Jan
J
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D051528:Guanylate Kinases; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008823:Micelles; D009703:Nucleoside-Phosphate Kinase / Q000378:metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D053676:Syntenins
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008823:Micelles; D019269:Phosphatidylinositol 4,5-Diphosphate; D011506:Proteins; D011993:Recombinant Fusion Proteins; C109621:SDCBP protein, human; D053676:Syntenins; C106868:CASK kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases; D017027:Protein Tyrosine Phosphatases