PDZ domain-phosphoinositide interactions in cell-signaling.
Proteins containing PDZ domains function as scaffolds for the formation and spatial confinement of large signaling complexes. They play an important role in the establishment and maintenance of cell polarity and neuronal connectivity. Therefore, they are intensively studied in the context of neurobiology and cancer. It is well established that PDZ domains are protein-interaction modules recognizing short peptide sequences generally situated at the C-terminal end of transmembrane receptors. Yet, it is not clear how those interactions are regulated. Our recent studies revealed that PDZ domains can also interact with phosphoinositides (PIPs), signaling lipids with key-roles in receptor signal transduction, membrane trafficking, cytoskeleton remodeling, subcellular compartmentalization and nuclear processes. In particular, we established that the PDZ domains of syntenin-1 and syntenin-2 bind to phosphatidylinositol 4, 5-bisphosphate (PIP2) with high-affinity. Syntenin-1/PIP2 interaction is important for receptor cargo recycling and syntenin-2 plays a role in the organization of nuclear PIP2. Those study cases indicate that cellular phosphoinositides might function as essential regulators of PDZ proteins. Here, we summarize and discuss our present knowledge about the occurrence, the biochemistry and the functionality of PDZ domain-lipid interactions.
Zimmermann
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Departement Menselijke Erfelijkheid, Laboratorium voor Glycobiologie en Ontwikkelingsgenetica-KULeuven, Vlaams Interuniversitair Instituut voor Biotechnologie, Herestraat 49, bus 602-B 3000 Leuven.
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D002450:Cell Communication / Q000502:physiology*; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008958:Models, Molecular; D010716:Phosphatidylinositols / Q000737:chemistry* / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D053676:Syntenins / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D047908:Intracellular Signaling Peptides and Proteins; D010716:Phosphatidylinositols; D053676:Syntenins