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Phosphoinositides and PDZ Domain Scaffolds

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Lipid-mediated Protein Signaling

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 991))

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

  1. Good MC, Zalatan JG, Lim WA (2011) Scaffold proteins: hubs for controlling the flow of cellular information. Science 332(6030):680–686

    PubMed  CAS  Google Scholar 

  2. 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

    PubMed  CAS  Google Scholar 

  3. Bilder D (2001) PDZ proteins and polarity: functions from the fly. Trends Genet 17(9):511–519

    PubMed  CAS  Google Scholar 

  4. Suzuki A, Ohno S (2006) The PAR-aPKC system: lessons in polarity. J Cell Sci 119(Pt 6):979–987

    PubMed  CAS  Google Scholar 

  5. 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

    PubMed  CAS  Google Scholar 

  6. Ponting CP, Phillips C (1995) DHR domains in syntrophins, neuronal NO synthases and other intracellular proteins. Trends Biochem Sci 20(3):102–103

    PubMed  CAS  Google Scholar 

  7. Kennedy MB (1995) Origin of PDZ (DHR, GLGF) domains. Trends Biochem Sci 20(9):350

    PubMed  CAS  Google Scholar 

  8. 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

    PubMed  CAS  Google Scholar 

  9. 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

    PubMed  CAS  Google Scholar 

  10. Giallourakis C et al (2006) A molecular-properties-based approach to understanding PDZ domain proteins and PDZ ligands. Genome Res 16(8):1056–1072

    PubMed  CAS  Google Scholar 

  11. 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

    Google Scholar 

  12. Morais Cabral JH et al (1996) Crystal structure of a PDZ domain. Nature 382(6592):649–652

    PubMed  CAS  Google Scholar 

  13. Kornau HC et al (1995) Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95. Science 269(5231):1737–1740

    PubMed  CAS  Google Scholar 

  14. 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

    PubMed  CAS  Google Scholar 

  15. Songyang Z et al (1997) Recognition of unique carboxyl-terminal motifs by distinct PDZ domains. Science 275(5296):73–77

    PubMed  CAS  Google Scholar 

  16. Stricker NL et al (1997) PDZ domain of neuronal nitric oxide synthase recognizes novel C-terminal peptide sequences. Nat Biotechnol 15(4):336–342

    PubMed  CAS  Google Scholar 

  17. Vaccaro P, Dente L (2002) PDZ domains: troubles in classification. FEBS Lett 512(1–3):345–349

    PubMed  CAS  Google Scholar 

  18. 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

    PubMed  CAS  Google Scholar 

  19. 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

    PubMed  CAS  Google Scholar 

  20. Hillier BJ et al (1999) Unexpected modes of PDZ domain scaffolding revealed by structure of nNOS-syntrophin complex. Science 284(5415):812–815

    PubMed  CAS  Google Scholar 

  21. 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

    PubMed  CAS  Google Scholar 

  22. 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

    PubMed  CAS  Google Scholar 

  23. 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

    PubMed  CAS  Google Scholar 

  24. 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

    PubMed  CAS  Google Scholar 

  25. Harris BZ, Lim WA (2001) Mechanism and role of PDZ domains in signaling complex assembly. J Cell Sci 114(Pt 18):3219–3231

    PubMed  CAS  Google Scholar 

  26. 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

    PubMed  CAS  Google Scholar 

  27. Harris BZ et al (2003) Role of electrostatic interactions in PDZ domain ligand recognition. Biochemistry 42(10):2797–2805

    PubMed  CAS  Google Scholar 

  28. Akiva E et al (2012) A dynamic view of domain-motif interactions. PLoS Comput Biol 8(1):e1002341

    PubMed  CAS  Google Scholar 

  29. Smock RG, Gierasch LM (2009) Sending signals dynamically. Science 324(5924):198–203

    PubMed  CAS  Google Scholar 

  30. Ivarsson Y (2012) Plasticity of PDZ domains in ligand recognition and signaling. FEBS Lett 586(17):2638–2647

    PubMed  CAS  Google Scholar 

  31. Irvine RF (2003) Nuclear lipid signalling. Nat Rev Mol Cell Biol 4(5):349–360

    PubMed  CAS  Google Scholar 

  32. Di Paolo G, De Camilli P (2006) Phosphoinositides in cell regulation and membrane dynamics. Nature 443(7112):651–657

    PubMed  Google Scholar 

  33. 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

    PubMed  CAS  Google Scholar 

  34. Balla T, Szentpetery Z, Kim YJ (2009) Phospho­inositide signaling: new tools and insights. Physiology (Bethesda) 24:231–244

    CAS  Google Scholar 

  35. Barlow CA, Laishram RS, Anderson RA (2010) Nuclear phosphoinositides: a signaling enigma wrapped in a compartmental conundrum. Trends Cell Biol 20(1):25–35

    PubMed  CAS  Google Scholar 

  36. Roth MG (2004) Phosphoinositides in constitutive membrane traffic. Physiol Rev 84(3):699–730

    PubMed  CAS  Google Scholar 

  37. Lassing I, Lindberg U (1985) Specific interaction between phosphatidylinositol 4,5-bisphosphate and profilactin. Nature 314(6010):472–474

    PubMed  CAS  Google Scholar 

  38. Whitman M et al (1988) Type I phosphatidylinositol kinase makes a novel inositol phospholipid, phosphatidylinositol-3-phosphate. Nature 332(6165):644–646

    PubMed  CAS  Google Scholar 

  39. Auger KR et al (1989) PDGF-dependent tyrosine phosphorylation stimulates production of novel polyphosphoinositides in intact cells. Cell 57(1):167–175

    PubMed  CAS  Google Scholar 

  40. Toker A, Cantley LC (1997) Signalling through the lipid products of phosphoinositide-3-OH kinase. Nature 387(6634):673–676

    PubMed  CAS  Google Scholar 

  41. 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

    PubMed  CAS  Google Scholar 

  42. Lemmon MA (2003) Phosphoinositide recognition domains. Traffic 4(4):201–213

    PubMed  CAS  Google Scholar 

  43. Balla T (2005) Inositol-lipid binding motifs: signal integrators through protein-lipid and protein-protein interactions. J Cell Sci 118(Pt 10):2093–2104

    PubMed  CAS  Google Scholar 

  44. Kutateladze TG (2010) Translation of the phosphoinositide code by PI effectors. Nat Chem Biol 6(7):507–513

    PubMed  CAS  Google Scholar 

  45. 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

    PubMed  CAS  Google Scholar 

  46. Mortier E et al (2005) Nuclear speckles and nucleoli targeting by PIP2-PDZ domain interactions. EMBO J 24(14):2556–2565

    PubMed  CAS  Google Scholar 

  47. Narayan K, Lemmon MA (2006) Determining selectivity of phosphoinositide-binding domains. Methods 39(2):122–133

    PubMed  CAS  Google Scholar 

  48. Rusten TE, Stenmark H (2006) Analyzing phosphoinositides and their interacting proteins. Nat Methods 3(4):251–258

    PubMed  CAS  Google Scholar 

  49. Varnai P, Balla T (2007) Visualization and manipulation of phosphoinositide dynamics in live cells using engineered protein domains. Pflugers Arch 455(1):69–82

    PubMed  CAS  Google Scholar 

  50. Wu H et al (2007) PDZ domains of Par-3 as potential phosphoinositide signaling integrators. Mol Cell 28(5):886–898

    PubMed  CAS  Google Scholar 

  51. 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

    PubMed  CAS  Google Scholar 

  52. Lemmon MA (2008) Membrane recognition by phospholipid-binding domains. Nat Rev Mol Cell Biol 9(2):99–111

    PubMed  CAS  Google Scholar 

  53. 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

    PubMed  CAS  Google Scholar 

  54. Yu JW et al (2004) Genome-wide analysis of membrane targeting by S. cerevisiae pleckstrin homology domains. Mol Cell 13(5):677–688

    PubMed  CAS  Google Scholar 

  55. 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

    Google Scholar 

  56. 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

    PubMed  CAS  Google Scholar 

  57. Zimmermann P et al (2005) Syndecan recycling [corrected] is controlled by syntenin-PIP2 interaction and Arf6. Dev Cell 9(3):377–388

    PubMed  CAS  Google Scholar 

  58. Baietti MF et al (2012) Syndecan-syntenin-ALIX regulates the biogenesis of exosomes. Nat Cell Biol 14(7):677–685

    PubMed  CAS  Google Scholar 

  59. 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

    PubMed  CAS  Google Scholar 

  60. 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

    PubMed  CAS  Google Scholar 

  61. 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

    PubMed  CAS  Google Scholar 

  62. Zwaal RF, Comfurius P, Bevers EM (2005) Surface exposure of phosphatidylserine in pathological cells. Cell Mol Life Sci 62(9):971–988

    PubMed  CAS  Google Scholar 

  63. Meerschaert K et al (2007) The tandem PDZ domains of syntenin promote cell invasion. Exp Cell Res 313(9):1790–1804

    PubMed  CAS  Google Scholar 

  64. Sugi T et al (2008) Structural insights into the PIP2 recognition by syntenin-1 PDZ domain. Biochem Biophys Res Commun 366(2):373–378

    PubMed  CAS  Google Scholar 

  65. 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

    CAS  Google Scholar 

  66. Zimmermann P (2006) The prevalence and significance of PDZ domain-phosphoinositide interactions. Biochim Biophys Acta 1761(8):947–956

    PubMed  CAS  Google Scholar 

  67. 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

    PubMed  CAS  Google Scholar 

  68. 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

    PubMed  CAS  Google Scholar 

  69. 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

    PubMed  CAS  Google Scholar 

  70. 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

    PubMed  CAS  Google Scholar 

  71. 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

    PubMed  CAS  Google Scholar 

  72. 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

    PubMed  CAS  Google Scholar 

  73. Erdmann KS (2003) The protein tyrosine phosphatase PTP-Basophil/Basophil-like. Interacting proteins and molecular functions. Eur J Biochem 270(24):4789–4798

    PubMed  CAS  Google Scholar 

  74. Abaan OD, Toretsky JA (2008) PTPL1: a large phosphatase with a split personality. Cancer Metastasis Rev 27(2):205–214

    PubMed  CAS  Google Scholar 

  75. 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

    PubMed  CAS  Google Scholar 

  76. 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

    PubMed  CAS  Google Scholar 

  77. 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

    PubMed  CAS  Google Scholar 

  78. Gallardo R et al (2010) Structural diversity of PDZ-lipid interactions. Chembiochem 11(4):456–467

    PubMed  CAS  Google Scholar 

  79. Xu J, Xia J (2006) Structure and function of PICK1. Neurosignals 15(4):190–201

    PubMed  CAS  Google Scholar 

  80. Malinow R, Malenka RC (2002) AMPA receptor trafficking and synaptic plasticity. Annu Rev Neurosci 25:103–126

    PubMed  CAS  Google Scholar 

  81. Malenka RC (2003) Synaptic plasticity and AMPA receptor trafficking. Ann N Y Acad Sci 1003:1–11

    PubMed  CAS  Google Scholar 

  82. Jin W et al (2006) Lipid binding regulates synaptic targeting of PICK1, AMPA receptor trafficking, and synaptic plasticity. J Neurosci 26(9):2380–2390

    PubMed  CAS  Google Scholar 

  83. 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

    PubMed  CAS  Google Scholar 

  84. Shi Y et al (2010) Redox-regulated lipid membrane binding of the PICK1 PDZ domain. Biochemistry 49(21):4432–4439

    PubMed  CAS  Google Scholar 

  85. 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

    PubMed  CAS  Google Scholar 

  86. Gonzalez-Mariscal L et al (2003) Tight junction proteins. Prog Biophys Mol Biol 81(1):1–44

    PubMed  CAS  Google Scholar 

  87. Ebnet K (2008) Organization of multiprotein complexes at cell-cell junctions. Histochem Cell Biol 130(1):1–20

    PubMed  CAS  Google Scholar 

  88. 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

    PubMed  CAS  Google Scholar 

  89. Islas S et al (2002) Nuclear localization of the tight junction protein ZO-2 in epithelial cells. Exp Cell Res 274(1):138–148

    PubMed  CAS  Google Scholar 

  90. 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

    PubMed  CAS  Google Scholar 

  91. 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

    PubMed  CAS  Google Scholar 

  92. 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

    PubMed  CAS  Google Scholar 

  93. 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

    PubMed  CAS  Google Scholar 

  94. 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

    PubMed  CAS  Google Scholar 

  95. Fanning AS et al (2007) Domain swapping within PDZ2 is responsible for dimerization of ZO proteins. J Biol Chem 282(52):37710–37716

    PubMed  CAS  Google Scholar 

  96. 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

    PubMed  CAS  Google Scholar 

  97. Wei X, Ellis HM (2001) Localization of the Drosophila MAGUK protein Polychaetoid is controlled by alternative splicing. Mech Dev 100(2):217–231

    PubMed  CAS  Google Scholar 

  98. 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

    PubMed  CAS  Google Scholar 

  99. 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

    PubMed  CAS  Google Scholar 

  100. 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

    PubMed  CAS  Google Scholar 

  101. 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

    PubMed  CAS  Google Scholar 

  102. 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

    PubMed  CAS  Google Scholar 

  103. Lambaerts K, Wilcox-Adelman SA, Zimmermann P (2009) The signaling mechanisms of syndecan heparan sulfate proteoglycans. Curr Opin Cell Biol 21(5):662–669

    PubMed  CAS  Google Scholar 

  104. 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

    PubMed  CAS  Google Scholar 

  105. Brown FD et al (2001) Phosphatidylinositol 4,5-bisphosphate and Arf6-regulated membrane traffic. J Cell Biol 154(5):1007–1017

    PubMed  CAS  Google Scholar 

  106. 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

    PubMed  CAS  Google Scholar 

  107. 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

    PubMed  CAS  Google Scholar 

  108. 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

    PubMed  CAS  Google Scholar 

  109. 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

    PubMed  CAS  Google Scholar 

  110. 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

    PubMed  CAS  Google Scholar 

  111. 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

    PubMed  CAS  Google Scholar 

  112. Chen X, Macara IG (2005) Par-3 controls tight junction assembly through the Rac exchange factor Tiam1. Nat Cell Biol 7(3):262–269

    PubMed  CAS  Google Scholar 

  113. 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

    PubMed  CAS  Google Scholar 

  114. Peck JW et al (2002) The RhoA-binding protein, rhophilin-2 regulates actin cytoskeleton organization. J Biol Chem 277(46):43924–43932

    PubMed  CAS  Google Scholar 

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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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