Abstract
The discovery that PSD-95/Discs large/ZO-1 (PDZ) domains can function as lipid-binding modules, in particular interacting with phosphoinositides (PIs), was made more than 10 years ago (Mol Cell 9(6): 1215–1225, 2002). Confirmatory studies and a series of functional follow-ups established PDZ domains as dual specificity modules displaying both peptide and lipid binding, and prompted a rethinking of the mode of action of PDZ domains in the control of cell signaling. In this chapter, after introducing PDZ domains, PIs and methods for studying protein-lipid interactions, we focus on (i) the prevalence and the specificity of PDZ-PIs interactions, (ii) the molecular determinants of PDZ-PIs interactions, (iii) the integration of lipid and peptide binding by PDZ domains, (iv) the common features of PIs interacting PDZ domains and (v) the regulation and functional significance of PDZ-PIs interactions.
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References
Good MC, Zalatan JG, Lim WA (2011) Scaffold proteins: hubs for controlling the flow of cellular information. Science 332(6030):680–686
Scott JD, Pawson T (2009) Cell signaling in space and time: where proteins come together and when they’re apart. Science 326(5957):1220–1224
Bilder D (2001) PDZ proteins and polarity: functions from the fly. Trends Genet 17(9):511–519
Suzuki A, Ohno S (2006) The PAR-aPKC system: lessons in polarity. J Cell Sci 119(Pt 6):979–987
Cho KO, Hunt CA, Kennedy MB (1992) The rat brain postsynaptic density fraction contains a homolog of the Drosophila discs-large tumor suppressor protein. Neuron 9(5):929–942
Ponting CP, Phillips C (1995) DHR domains in syntrophins, neuronal NO synthases and other intracellular proteins. Trends Biochem Sci 20(3):102–103
Kennedy MB (1995) Origin of PDZ (DHR, GLGF) domains. Trends Biochem Sci 20(9):350
Woods DF, Bryant PJ (1993) ZO-1, DlgA and PSD-95/SAP90: homologous proteins in tight, septate and synaptic cell junctions. Mech Dev 44(2–3):85–89
Kim E et al (1995) Clustering of Shaker-type K + channels by interaction with a family of membrane-associated guanylate kinases. Nature 378(6552):85–88
Giallourakis C et al (2006) A molecular-properties-based approach to understanding PDZ domain proteins and PDZ ligands. Genome Res 16(8):1056–1072
te Velthuis AJ et al (2011) Genome-wide analysis of PDZ domain binding reveals inherent functional overlap within the PDZ interaction network. PLoS One 6(1):e16047
Morais Cabral JH et al (1996) Crystal structure of a PDZ domain. Nature 382(6592):649–652
Kornau HC et al (1995) Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95. Science 269(5231):1737–1740
Niethammer M, Kim E, Sheng M (1996) Interaction between the C terminus of NMDA receptor subunits and multiple members of the PSD-95 family of membrane-associated guanylate kinases. J Neurosci 16(7):2157–2163
Songyang Z et al (1997) Recognition of unique carboxyl-terminal motifs by distinct PDZ domains. Science 275(5296):73–77
Stricker NL et al (1997) PDZ domain of neuronal nitric oxide synthase recognizes novel C-terminal peptide sequences. Nat Biotechnol 15(4):336–342
Vaccaro P, Dente L (2002) PDZ domains: troubles in classification. FEBS Lett 512(1–3):345–349
Doyle DA et al (1996) Crystal structures of a complexed and peptide-free membrane protein-binding domain: molecular basis of peptide recognition by PDZ. Cell 85(7):1067–1076
Daniels DL et al (1998) Crystal structure of the hCASK PDZ domain reveals the structural basis of class II PDZ domain target recognition. Nat Struct Biol 5(4):317–325
Hillier BJ et al (1999) Unexpected modes of PDZ domain scaffolding revealed by structure of nNOS-syntrophin complex. Science 284(5415):812–815
Feng W et al (2002) PDZ7 of glutamate receptor interacting protein binds to its target via a novel hydrophobic surface area. J Biol Chem 277(43):41140–41146
Xu XZ et al (1998) Coordination of an array of signaling proteins through homo- and heteromeric interactions between PDZ domains and target proteins. J Cell Biol 142(2):545–555
Lau AG, Hall RA (2001) Oligomerization of NHERF-1 and NHERF-2 PDZ domains: differential regulation by association with receptor carboxyl-termini and by phosphorylation. Biochemistry 40(29):8572–8580
Chang BH et al (2011) A systematic family-wide investigation reveals that 30 % of mammalian PDZ domains engage in PDZ-PDZ interactions. Chem Biol 18(9):1143–1152
Harris BZ, Lim WA (2001) Mechanism and role of PDZ domains in signaling complex assembly. J Cell Sci 114(Pt 18):3219–3231
Chi CN et al (2006) Two conserved residues govern the salt and pH dependencies of the binding reaction of a PDZ domain. J Biol Chem 281(48):36811–36818
Harris BZ et al (2003) Role of electrostatic interactions in PDZ domain ligand recognition. Biochemistry 42(10):2797–2805
Akiva E et al (2012) A dynamic view of domain-motif interactions. PLoS Comput Biol 8(1):e1002341
Smock RG, Gierasch LM (2009) Sending signals dynamically. Science 324(5924):198–203
Ivarsson Y (2012) Plasticity of PDZ domains in ligand recognition and signaling. FEBS Lett 586(17):2638–2647
Irvine RF (2003) Nuclear lipid signalling. Nat Rev Mol Cell Biol 4(5):349–360
Di Paolo G, De Camilli P (2006) Phosphoinositides in cell regulation and membrane dynamics. Nature 443(7112):651–657
Bunce MW, Bergendahl K, Anderson RA (2006) Nuclear PI(4,5)P(2): a new place for an old signal. Biochim Biophys Acta 1761(5–6):560–569
Balla T, Szentpetery Z, Kim YJ (2009) Phosphoinositide signaling: new tools and insights. Physiology (Bethesda) 24:231–244
Barlow CA, Laishram RS, Anderson RA (2010) Nuclear phosphoinositides: a signaling enigma wrapped in a compartmental conundrum. Trends Cell Biol 20(1):25–35
Roth MG (2004) Phosphoinositides in constitutive membrane traffic. Physiol Rev 84(3):699–730
Lassing I, Lindberg U (1985) Specific interaction between phosphatidylinositol 4,5-bisphosphate and profilactin. Nature 314(6010):472–474
Whitman M et al (1988) Type I phosphatidylinositol kinase makes a novel inositol phospholipid, phosphatidylinositol-3-phosphate. Nature 332(6165):644–646
Auger KR et al (1989) PDGF-dependent tyrosine phosphorylation stimulates production of novel polyphosphoinositides in intact cells. Cell 57(1):167–175
Toker A, Cantley LC (1997) Signalling through the lipid products of phosphoinositide-3-OH kinase. Nature 387(6634):673–676
Ma L et al (1998) Corequirement of specific phosphoinositides and small GTP-binding protein Cdc42 in inducing actin assembly in Xenopus egg extracts. J Cell Biol 140(5):1125–1136
Lemmon MA (2003) Phosphoinositide recognition domains. Traffic 4(4):201–213
Balla T (2005) Inositol-lipid binding motifs: signal integrators through protein-lipid and protein-protein interactions. J Cell Sci 118(Pt 10):2093–2104
Kutateladze TG (2010) Translation of the phosphoinositide code by PI effectors. Nat Chem Biol 6(7):507–513
Zimmermann P et al (2002) PIP(2)-PDZ domain binding controls the association of syntenin with the plasma membrane. Mol Cell 9(6):1215–1225
Mortier E et al (2005) Nuclear speckles and nucleoli targeting by PIP2-PDZ domain interactions. EMBO J 24(14):2556–2565
Narayan K, Lemmon MA (2006) Determining selectivity of phosphoinositide-binding domains. Methods 39(2):122–133
Rusten TE, Stenmark H (2006) Analyzing phosphoinositides and their interacting proteins. Nat Methods 3(4):251–258
Varnai P, Balla T (2007) Visualization and manipulation of phosphoinositide dynamics in live cells using engineered protein domains. Pflugers Arch 455(1):69–82
Wu H et al (2007) PDZ domains of Par-3 as potential phosphoinositide signaling integrators. Mol Cell 28(5):886–898
Ivarsson Y et al (2011) Cooperative phosphoinositide and peptide binding by PSD-95/discs large/ZO-1 (PDZ) domain of polychaetoid, Drosophila zonulin. J Biol Chem 286(52):44669–44678
Lemmon MA (2008) Membrane recognition by phospholipid-binding domains. Nat Rev Mol Cell Biol 9(2):99–111
Yu JW, Lemmon MA (2001) All phox homology (PX) domains from Saccharomyces cerevisiae specifically recognize phosphatidylinositol 3-phosphate. J Biol Chem 276(47):44179–44184
Yu JW et al (2004) Genome-wide analysis of membrane targeting by S. cerevisiae pleckstrin homology domains. Mol Cell 13(5):677–688
Ivarsson Y et al (2013) Prevalence, specificity and determinants of lipid-interacting PDZ domains from an in-cell screen and in vitro binding experiments. PLoS One 8(2):e54581
Chen Y et al (2012) Genome-wide functional annotation of dual-specificity protein- and lipid-binding modules that regulate protein interactions. Mol Cell 46(2):226–237
Zimmermann P et al (2005) Syndecan recycling [corrected] is controlled by syntenin-PIP2 interaction and Arf6. Dev Cell 9(3):377–388
Baietti MF et al (2012) Syndecan-syntenin-ALIX regulates the biogenesis of exosomes. Nat Cell Biol 14(7):677–685
Grootjans JJ et al (1997) Syntenin, a PDZ protein that binds syndecan cytoplasmic domains. Proc Natl Acad Sci U S A 94(25):13683–13688
Grootjans JJ et al (2000) Syntenin-syndecan binding requires syndecan-synteny and the co-operation of both PDZ domains of syntenin. J Biol Chem 275(26):19933–19941
Varnai P, Balla T (1998) Visualization of phosphoinositides that bind pleckstrin homology domains: calcium- and agonist-induced dynamic changes and relationship to myo-[3H]inositol-labeled phosphoinositide pools. J Cell Biol 143(2):501–510
Zwaal RF, Comfurius P, Bevers EM (2005) Surface exposure of phosphatidylserine in pathological cells. Cell Mol Life Sci 62(9):971–988
Meerschaert K et al (2007) The tandem PDZ domains of syntenin promote cell invasion. Exp Cell Res 313(9):1790–1804
Sugi T et al (2008) Structural insights into the PIP2 recognition by syntenin-1 PDZ domain. Biochem Biophys Res Commun 366(2):373–378
Wawrzyniak AM et al (2012) Extensions of PSD-95/discs large/ZO-1 (PDZ) domains influence lipid binding and membrane targeting of syntenin-1. FEBS Lett 586(10):1445–1451
Zimmermann P (2006) The prevalence and significance of PDZ domain-phosphoinositide interactions. Biochim Biophys Acta 1761(8):947–956
Borrell-Pages M et al (2000) The carboxy-terminal cysteine of the tetraspanin L6 antigen is required for its interaction with SITAC, a novel PDZ protein. Mol Biol Cell 11(12):4217–4225
Koroll M, Rathjen FG, Volkmer H (2001) The neural cell recognition molecule neurofascin interacts with syntenin-1 but not with syntenin-2, both of which reveal self-associating activity. J Biol Chem 276(14):10646–10654
Suzuki A et al (2001) Atypical protein kinase C is involved in the evolutionarily conserved par protein complex and plays a critical role in establishing epithelia-specific junctional structures. J Cell Biol 152(6):1183–1196
Banville D et al (1994) A novel protein-tyrosine phosphatase with homology to both the cytoskeletal proteins of the band 4.1 family and junction-associated guanylate kinases. J Biol Chem 269(35):22320–22327
Maekawa K et al (1994) Molecular cloning of a novel protein-tyrosine phosphatase containing a membrane-binding domain and GLGF repeats. FEBS Lett 337(2):200–206
Saras J et al (1994) Cloning and characterization of PTPL1, a protein tyrosine phosphatase with similarities to cytoskeletal-associated proteins. J Biol Chem 269(39):24082–24089
Erdmann KS (2003) The protein tyrosine phosphatase PTP-Basophil/Basophil-like. Interacting proteins and molecular functions. Eur J Biochem 270(24):4789–4798
Abaan OD, Toretsky JA (2008) PTPL1: a large phosphatase with a split personality. Cancer Metastasis Rev 27(2):205–214
Kozlov G, Gehring K, Ekiel I (2000) Solution structure of the PDZ2 domain from human phosphatase hPTP1E and its interactions with C-terminal peptides from the Fas receptor. Biochemistry 39(10):2572–2580
Erdmann KS et al (2000) The Adenomatous Polyposis Coli-protein (APC) interacts with the protein tyrosine phosphatase PTP-BL via an alternatively spliced PDZ domain. Oncogene 19(34):3894–3901
Kachel N et al (2003) Structure determination and ligand interactions of the PDZ2b domain of PTP-Bas (hPTP1E): splicing-induced modulation of ligand specificity. J Mol Biol 334(1):143–155
Gallardo R et al (2010) Structural diversity of PDZ-lipid interactions. Chembiochem 11(4):456–467
Xu J, Xia J (2006) Structure and function of PICK1. Neurosignals 15(4):190–201
Malinow R, Malenka RC (2002) AMPA receptor trafficking and synaptic plasticity. Annu Rev Neurosci 25:103–126
Malenka RC (2003) Synaptic plasticity and AMPA receptor trafficking. Ann N Y Acad Sci 1003:1–11
Jin W et al (2006) Lipid binding regulates synaptic targeting of PICK1, AMPA receptor trafficking, and synaptic plasticity. J Neurosci 26(9):2380–2390
Pan L et al (2007) Clustering and synaptic targeting of PICK1 requires direct interaction between the PDZ domain and lipid membranes. EMBO J 26(21):4576–4587
Shi Y et al (2010) Redox-regulated lipid membrane binding of the PICK1 PDZ domain. Biochemistry 49(21):4432–4439
Gonzalez-Mariscal L, Betanzos A, Avila-Flores A (2000) MAGUK proteins: structure and role in the tight junction. Semin Cell Dev Biol 11(4):315–324
Gonzalez-Mariscal L et al (2003) Tight junction proteins. Prog Biophys Mol Biol 81(1):1–44
Ebnet K (2008) Organization of multiprotein complexes at cell-cell junctions. Histochem Cell Biol 130(1):1–20
Betanzos A et al (2004) The tight junction protein ZO-2 associates with Jun, Fos and C/EBP transcription factors in epithelial cells. Exp Cell Res 292(1):51–66
Islas S et al (2002) Nuclear localization of the tight junction protein ZO-2 in epithelial cells. Exp Cell Res 274(1):138–148
Traweger A et al (2003) The tight junction protein ZO-2 localizes to the nucleus and interacts with the heterogeneous nuclear ribonucleoprotein scaffold attachment factor-B. J Biol Chem 278(4):2692–2700
Willott E et al (1993) The tight junction protein ZO-1 is homologous to the Drosophila discs-large tumor suppressor protein of septate junctions. Proc Natl Acad Sci U S A 90(16):7834–7838
Beatch M et al (1996) The tight junction protein ZO-2 contains three PDZ (PSD-95/Discs-Large/ZO-1) domains and an alternatively spliced region. J Biol Chem 271(42):25723–25726
Haskins J et al (1998) ZO-3, a novel member of the MAGUK protein family found at the tight junction, interacts with ZO-1 and occludin. J Cell Biol 141(1):199–208
Meerschaert K et al (2009) The PDZ2 domain of zonula occludens-1 and −2 is a phosphoinositide binding domain. Cell Mol Life Sci 66(24):3951–3966
Fanning AS et al (2007) Domain swapping within PDZ2 is responsible for dimerization of ZO proteins. J Biol Chem 282(52):37710–37716
Giepmans BN, Verlaan I, Moolenaar WH (2001) Connexin-43 interactions with ZO-1 and alpha- and beta-tubulin. Cell Commun Adhes 8(4–6):219–223
Wei X, Ellis HM (2001) Localization of the Drosophila MAGUK protein Polychaetoid is controlled by alternative splicing. Mech Dev 100(2):217–231
Choi W et al (2011) The single Drosophila ZO-1 protein Polychaetoid regulates embryonic morphogenesis in coordination with Canoe/afadin and Enabled. Mol Biol Cell 22(12):2010–2030
Jung AC et al (2006) Polychaetoid/ZO-1 is required for cell specification and rearrangement during Drosophila tracheal morphogenesis. Curr Biol 16(12):1224–1231
Adams ME et al (1993) Two forms of mouse syntrophin, a 58 kd dystrophin-associated protein, differ in primary structure and tissue distribution. Neuron 11(3):531–540
Yan J et al (2005) Structure of the split PH domain and distinct lipid-binding properties of the PH-PDZ supramodule of alpha-syntrophin. EMBO J 24(23):3985–3995
Zimmermann P et al (2001) Characterization of syntenin, a syndecan-binding PDZ protein, as a component of cell adhesion sites and microfilaments. Mol Biol Cell 12(2):339–350
Lambaerts K, Wilcox-Adelman SA, Zimmermann P (2009) The signaling mechanisms of syndecan heparan sulfate proteoglycans. Curr Opin Cell Biol 21(5):662–669
Honda A et al (1999) Phosphatidylinositol 4-phosphate 5-kinase alpha is a downstream effector of the small G protein ARF6 in membrane ruffle formation. Cell 99(5):521–532
Brown FD et al (2001) Phosphatidylinositol 4,5-bisphosphate and Arf6-regulated membrane traffic. J Cell Biol 154(5):1007–1017
Lambaerts K et al (2012) Syntenin, a syndecan adaptor and an Arf6 phosphatidylinositol 4,5-bisphosphate effector, is essential for epiboly and gastrulation cell movements in zebrafish. J Cell Sci 125 (Pt 5):1129–1140
Cocco L et al (1988) Rapid changes in phospholipid metabolism in the nuclei of Swiss 3T3 cells induced by treatment of the cells with insulin-like growth factor I. Biochem Biophys Res Commun 154(3):1266–1272
Divecha N, Banfic H, Irvine RF (1991) The polyphosphoinositide cycle exists in the nuclei of Swiss 3T3 cells under the control of a receptor (for IGF-I) in the plasma membrane, and stimulation of the cycle increases nuclear diacylglycerol and apparently induces translocation of protein kinase C to the nucleus. EMBO J 10(11):3207–3214
Li W et al (2012) Star-PAP control of BIK expression and apoptosis is regulated by nuclear PIPKIalpha and PKCdelta signaling. Mol Cell 45(1):25–37
Peters PJ et al (1995) Overexpression of wild-type and mutant ARF1 and ARF6: distinct perturbations of nonoverlapping membrane compartments. J Cell Biol 128(6):1003–1017
Varnai P et al (2006) Rapidly inducible changes in phosphatidylinositol 4,5-bisphosphate levels influence multiple regulatory functions of the lipid in intact living cells. J Cell Biol 175(3):377–382
Chen X, Macara IG (2005) Par-3 controls tight junction assembly through the Rac exchange factor Tiam1. Nat Cell Biol 7(3):262–269
Watanabe G et al (1996) Protein kinase N (PKN) and PKN-related protein rhophilin as targets of small GTPase Rho. Science 271(5249):645–648
Peck JW et al (2002) The RhoA-binding protein, rhophilin-2 regulates actin cytoskeleton organization. J Biol Chem 277(46):43924–43932
Acknowledgments
The laboratories of P.Z. are supported by the Fund for Scientific Research-Flanders (FWO), the Concerted Actions Program of the Katholieke Universiteit Leuven, the Belgian Federation Against Cancer (Stichting Tegen Kanker), the Interuniversity Attraction poles of the Prime Ministers Services (IUAP), and the EMBO young investigator program (to P.Z.). A.M.W. is supported by a Ph.D. fellowship from FWO.
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Wawrzyniak, A.M., Kashyap, R., Zimmermann, P. (2013). Phosphoinositides and PDZ Domain Scaffolds. In: Capelluto, D. (eds) Lipid-mediated Protein Signaling. Advances in Experimental Medicine and Biology, vol 991. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6331-9_4
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