Most functions of eukaryotic cells are controlled by cellular membranes, which are not static entities but undergo frequent budding, fission, fusion, and sculpting reactions collectively referred to as membrane dynamics. Consequently, regulation of membrane dynamics is crucial for cellular functions. A key mechanism in such regulation is the reversible recruitment of cytosolic proteins or protein complexes to specific membranes at specific time points. To a large extent this recruitment is orchestrated by phosphorylated derivatives of the membrane lipid phosphatidylinositol, known as phosphoinositides. The seven phosphoinositides found in nature localize to distinct membrane domains and recruit distinct effectors, thereby contributing strongly to the maintenance of membrane identity. Many of the phosphoinositide effectors are proteins that control membrane dynamics, and in this review we discuss the functions of phosphoinositides in membrane dynamics during exocytosis, endocytosis, autophagy, cell division, cell migration, and epithelial cell polarity, with emphasis on protein effectors that are recruited by specific phosphoinositides during these processes.


Article metrics loading...

Loading full text...

Full text loading...


Literature Cited

  1. Alliouachene S, Bilanges B, Chicanne G, Anderson KE, Pearce W. et al. 2015. Inactivation of the class II PI3K-C2uβ potentiates insulin signaling and sensitivity. Cell Rep. 13:1881–94 [Google Scholar]
  2. Axe EL, Walker SA, Manifava M, Chandra P, Roderick HL. et al. 2008. Autophagosome formation from compartments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum. J. Cell Biol. 182:685–701 [Google Scholar]
  3. Balla T. 2013. Phosphoinositides: tiny lipids with giant impact on cell regulation. Physiol. Rev. 93:1019–137 [Google Scholar]
  4. Blumental-Perry A, Haney CJ, Weixel KM, Watkins SC, Weisz OA, Aridor M. 2006. Phosphatidylinositol 4-phosphate formation at ER exit sites regulates ER export. Dev. Cell 11:671–82 [Google Scholar]
  5. Boal F, Mansour R, Gayral M, Saland E, Chicanne G. et al. 2015. TOM1 is a PI5P effector involved in the regulation of endosomal maturation. J. Cell Sci. 128:815–27 [Google Scholar]
  6. Bohdanowicz M, Balkin DM, De CP, Grinstein S. 2012. Recruitment of OCRL and Inpp5B to phagosomes by Rab5 and APPL1 depletes phosphoinositides and attenuates Akt signaling. Mol. Biol. Cell 23:176–87 [Google Scholar]
  7. Botelho RJ, Teruel M, Dierckman R, Anderson R, Wells A. et al. 2000. Localized biphasic changes in phosphatidylinositol-4,5-bisphosphate at sites of phagocytosis. J. Cell Biol. 151:1353–68 [Google Scholar]
  8. Boucrot E, Ferreira AP, Almeida-Souza L, Debard S, Vallis Y. et al. 2015. Endophilin marks and controls a clathrin-independent endocytic pathway. Nature 517:460–65 [Google Scholar]
  9. Bretscher A, Edwards K, Fehon RG. 2002. ERM proteins and merlin: integrators at the cell cortex. Nat. Rev. Mol. Cell Biol. 3:586–99 [Google Scholar]
  10. Brill JA, Wong R, Wilde A. 2011. Phosphoinositide function in cytokinesis. Curr. Biol. 21:R930–34 [Google Scholar]
  11. Carlton J, Bujny M, Peter BJ, Oorschot VM, Rutherford A. et al. 2004. Sorting nexin-1 mediates tubular endosome-to-TGN transport through coincidence sensing of high-curvature membranes and 3-phosphoinositides. Curr. Biol. 14:1791–800 [Google Scholar]
  12. Carlton JG, Martin-Serrano J. 2007. Parallels between cytokinesis and retroviral budding: a role for the ESCRT machinery. Science 316:1908–12 [Google Scholar]
  13. Cauvin C, Echard A. 2015. Phosphoinositides: lipids with informative heads and mastermind functions in cell division. Biochim. Biophys. Acta 1851:832–43 [Google Scholar]
  14. Charpentier E. 2015. CRISPR-Cas9: how research on a bacterial RNA-guided mechanism opened new perspectives in biotechnology and biomedicine. EMBO Mol. Med. 7:363–65 [Google Scholar]
  15. Christoforidis S, Miaczynska M, Ashman K, Wilm M, Zhao L. et al. 1999. Phosphatidylinositol-3-OH kinases are Rab5 effectors. Nat. Cell Biol. 1:249–52 [Google Scholar]
  16. Chu BB, Liao YC, Qi W, Xie C, Du X. et al. 2015. Cholesterol transport through lysosome-peroxisome membrane contacts. Cell 161:291–306 [Google Scholar]
  17. Codogno P, Mehrpour M, Proikas-Cezanne T. 2012. Canonical and non-canonical autophagy: variations on a common theme of self-eating?. Nat. Rev. Mol. Cell Biol. 13:7–12 [Google Scholar]
  18. Conner SD, Schmid SL. 2003. Regulated portals of entry into the cell. Nature 422:37–44 [Google Scholar]
  19. Corgan AM, Singleton C, Santoso CB, Greenwood JA. 2004. Phosphoinositides differentially regulate alpha-actinin flexibility and function. Biochem. J. 378:1067–72 [Google Scholar]
  20. Cote JF, Motoyama AB, Bush JA, Vuori K. 2005. A novel and evolutionarily conserved PtdIns(3,4,5)P3-binding domain is necessary for DOCK180 signalling. Nat. Cell Biol. 7:797–807 [Google Scholar]
  21. Cremona O, Di Paolo G, Wenk MR, Lüthi A, Kim WT. et al. 1999. Essential role of phosphoinositide metabolism in synaptic vesicle recycling. Cell 99:179–88 [Google Scholar]
  22. Croise P, Estay-Ahumada C, Gasman S, Ory S. 2014. Rho GTPases, phosphoinositides, and actin: a tripartite framework for efficient vesicular trafficking. Small GTPases 5:e29469 [Google Scholar]
  23. de Saint-Jean M, Delfosse V, Douguet D, Chicanne G, Payrastre B. et al. 2011. Osh4p exchanges sterols for phosphatidylinositol 4-phosphate between lipid bilayers. J. Cell Biol. 195:965–78 [Google Scholar]
  24. Di Paolo G, De Camilli P. 2006. Phosphoinositides in cell regulation and membrane dynamics. Nature 443:651–57 [Google Scholar]
  25. Fabrowski P, Necakov AS, Mumbauer S, Loeser E, Reversi A. et al. 2013. Tubular endocytosis drives remodelling of the apical surface during epithelial morphogenesis in Drosophila. Nat. Commun. 4:2244 [Google Scholar]
  26. Fernandez-Borja M, Wubbolts R, Calafat J, Janssen H, Divecha N. et al. 1999. Multivesicular body morphogenesis requires phosphatidylinositol 3-kinase activity. Curr. Biol. 14:55–58 [Google Scholar]
  27. Fields IC, King SM, Shteyn E, Kang RS, Folsch H. 2010. Phosphatidylinositol 3,4,5-trisphosphate localization in recycling endosomes is necessary for AP-1B-dependent sorting in polarized epithelial cells. Mol. Biol. Cell 21:95–105 [Google Scholar]
  28. Fili N, Calleja V, Woscholski R, Parker PJ, Larijani B. 2006. Compartmental signal modulation: Endosomal phosphatidylinositol 3-phosphate controls endosome morphology and selective cargo sorting. PNAS 103:15473–78 [Google Scholar]
  29. Flores-Rodriguez N, Kenwright DA, Chung PH, Harrison AW, Stefani F. et al. 2015. ESCRT-0 marks an APPL1-independent transit route for EGFR between the cell surface and the EEA1-positive early endosome. J. Cell Sci. 128:755–67 [Google Scholar]
  30. Ford MG, Pearse BM, Higgins MK, Vallis Y, Owen DJ. et al. 2001. Simultaneous binding of PtdIns(4,5)P2 and clathrin by AP180 in the nucleation of clathrin lattices on membranes. Science 291:1051–55 [Google Scholar]
  31. Francis MK, Holst MR, Vidal-Quadras M, Henriksson S, Santarella-Mellwig R. et al. 2015. Endocytic membrane turnover at the leading edge is driven by a transient interaction between Cdc42 and GRAF1. J. Cell Sci. 128:4183–95 [Google Scholar]
  32. Franco I, Gulluni F, Campa CC, Costa C, Margaria JP. et al. 2014. PI3K class II alpha controls spatially restricted endosomal PtdIns3P and Rab11 activation to promote primary cilium function. Dev. Cell 28:647–58 [Google Scholar]
  33. Funderburk SF, Wang QJ, Yue Z. 2010. The Beclin 1–VPS34 complex—at the crossroads of autophagy and beyond. Trends Cell Biol. 20:355–62 [Google Scholar]
  34. Gold ES, Underhill DM, Morrissette NS, Guo J, McNiven MA, Aderem A. 1999. Dynamin 2 is required for phagocytosis in macrophages. J. Exp. Med. 190:1849–56 [Google Scholar]
  35. Grimmel M, Backhaus C, Proikas-Cezanne T. 2015. WIPI-mediated autophagy and longevity. Cells 4:202–17 [Google Scholar]
  36. Hall AB, Gakidis MA, Glogauer M, Wilsbacher JL, Gao S. et al. 2006. Requirements for Vav guanine nucleotide exchange factors and Rho GTPases in FcγR- and complement-mediated phagocytosis. Immunity 24:305–16 [Google Scholar]
  37. Hamasaki M, Furuta N, Matsuda A, Nezu A, Yamamoto A. et al. 2013. Autophagosomes form at ER-mitochondria contact sites. Nature 495:389–93 [Google Scholar]
  38. Hammond GR, Balla T. 2015. Polyphosphoinositide binding domains: key to inositol lipid biology. Biochim. Biophys. Acta 1851:746–58 [Google Scholar]
  39. Han J, Luby-Phelps K, Das B, Shu X, Xia Y. et al. 1998. Role of substrates and products of PI 3-kinase in regulating activation of Rac-related guanosine triphosphatases by Vav. Science 279:558–60 [Google Scholar]
  40. Hattula K, Furuhjelm J, Arffman A, Peranen J. 2002. A Rab8-specific GDP/GTP exchange factor is involved in actin remodeling and polarized membrane transport. Mol. Biol. Cell 13:3268–80 [Google Scholar]
  41. He B, Xi F, Zhang X, Zhang J, Guo W. 2007. Exo70 interacts with phospholipids and mediates the targeting of the exocyst to the plasma membrane. EMBO J. 26:4053–65 [Google Scholar]
  42. He Y, Deng YZ, Naqvi NI. 2013. Atg24-assisted mitophagy in the foot cells is necessary for proper asexual differentiation in Magnaporthe oryzae. Autophagy 9:1818–27 [Google Scholar]
  43. Henley JR, Krueger EW, Oswald BJ, McNiven MA. 1998. Dynamin-mediated internalization of caveolae. J. Cell Biol. 141:85–99 [Google Scholar]
  44. Henne WM, Boucrot E, Meinecke M, Evergren E, Vallis Y. et al. 2010. FCHo proteins are nucleators of clathrin-mediated endocytosis. Science 328:1281–84 [Google Scholar]
  45. Hille B, Dickson EJ, Kruse M, Vivas O, Suh BC. 2015. Phosphoinositides regulate ion channels. Biochim. Biophys. Acta 1851:844–56 [Google Scholar]
  46. Hirst J, Borner GH, Edgar J, Hein MY, Mann M. et al. 2013. Interaction between AP-5 and the hereditary spastic paraplegia proteins SPG11 and SPG15. Mol. Biol. Cell 24:2558–69 [Google Scholar]
  47. Ho CY, Choy CH, Wattson CA, Johnson DE, Botelho RJ. 2015. The Fab1/PIKfyve phosphoinositide phosphate kinase is not necessary to maintain the pH of lysosomes and of the yeast vacuole. J. Biol. Chem. 290:9919–28 [Google Scholar]
  48. Hoepfner S, Severin F, Cabezas A, Habermann B, Runge A. et al. 2005. Modulation of receptor recycling and degradation by the endosomal kinesin KIF16B. Cell 121:437–50 [Google Scholar]
  49. Hollopeter G, Lange JJ, Zhang Y, Vu TN, Gu M. et al. 2014. The membrane-associated proteins FCHo and SGIP are allosteric activators of the AP2 clathrin adaptor complex. eLife 3:e03648 [Google Scholar]
  50. Hunt SD, Townley AK, Danson CM, Cullen PJ, Stephens DJ. 2013. Microtubule motors mediate endosomal sorting by maintaining functional domain organization. J. Cell Sci. 126:2493–501 [Google Scholar]
  51. Idevall-Hagren O, Lu A, Xie B, De CP. 2015. Triggered Ca2+ influx is required for extended synaptotagmin 1–induced ER–plasma membrane tethering. EMBO J. 34:2291–305 [Google Scholar]
  52. Innocenti M, Frittoli E, Ponzanelli I, Falck JR, Brachmann SM. et al. 2003. Phosphoinositide 3-kinase activates Rac by entering in a complex with Eps8, Abi1, and Sos-1. J. Cell Biol. 160:17–23 [Google Scholar]
  53. Itoh T, Koshiba S, Kigawa T, Kikuchi A, Yokoyama S, Takenawa T. 2001. Role of the ENTH domain in phosphatidylinositol-4,5-bisphosphate binding and endocytosis. Science 291:1047–51 [Google Scholar]
  54. Jeschke A, Zehethofer N, Lindner B, Krupp J, Schwudke D. et al. 2015. Phosphatidylinositol 4-phosphate and phosphatidylinositol 3-phosphate regulate phagolysosome biogenesis. PNAS 112:4636–41 [Google Scholar]
  55. Jin Y, Sultana A, Gandhi P, Franklin E, Hamamoto S. et al. 2011. Myosin V transports secretory vesicles via a Rab GTPase cascade and interaction with the exocyst complex. Dev. Cell 21:1156–70 [Google Scholar]
  56. Jongsma ML, Berlin I, Neefjes J. 2015. On the move: organelle dynamics during mitosis. Trends Cell Biol. 25:112–24 [Google Scholar]
  57. Kamen LA, Levinsohn J, Swanson JA. 2007. Differential association of phosphatidylinositol 3-kinase, SHIP-1, and PTEN with forming phagosomes. Mol. Biol. Cell 18:2463–72 [Google Scholar]
  58. Karimzadeh F, Primeau M, Mountassif D, Rouiller I, Lamarche-Vane N. 2012. A stretch of polybasic residues mediates Cdc42 GTPase-activating protein (CdGAP) binding to phosphatidylinositol 3,4,5-trisphosphate and regulates its GAP activity. J. Biol. Chem. 287:19610–21 [Google Scholar]
  59. Karunakaran S, Sasser T, Rajalekshmi S, Fratti RA. 2012. SNAREs, HOPS and regulatory lipids control the dynamics of vacuolar actin during homotypic fusion in S. cerevisiae. J. Cell Sci. 125:1683–92 [Google Scholar]
  60. Ketel K, Krauss M, Nicot AS, Puchkov D, Wieffer M. et al. 2016. A phosphoinositide conversion mechanism for exit from endosomes. Nature 529:408–12 [Google Scholar]
  61. Khundadze M, Kollmann K, Koch N, Biskup C, Nietzsche S. et al. 2013. A hereditary spastic paraplegia mouse model supports a role of ZFYVE26/SPASTIZIN for the endolysosomal system. PLOS Genet. 9:e1003988 [Google Scholar]
  62. Kim GH, Dayam RM, Prashar A, Terebiznik M, Botelho RJ. 2014. PIKfyve inhibition interferes with phagosome and endosome maturation in macrophages. Traffic 15:1143–63 [Google Scholar]
  63. Knodler A, Feng S, Zhang J, Zhang X, Das A. et al. 2010. Coordination of Rab8 and Rab11 in primary ciliogenesis. PNAS 107:6346–51 [Google Scholar]
  64. Kobayashi S, Shirai T, Kiyokawa E, Mochizuki N, Matsuda M, Fukui Y. 2001. Membrane recruitment of DOCK180 by binding to PtdIns(3,4,5)P3. Biochem. J. 354:73–78 [Google Scholar]
  65. Krahn MP, Klopfenstein DR, Fischer N, Wodarz A. 2010. Membrane targeting of Bazooka/PAR-3 is mediated by direct binding to phosphoinositide lipids. Curr. Biol. 20:636–42 [Google Scholar]
  66. Krause M, Gautreau A. 2014. Steering cell migration: lamellipodium dynamics and the regulation of directional persistence. Nat. Rev. Mol. Cell Biol. 15:577–90 [Google Scholar]
  67. Larijani B, Poccia DL. 2009. Nuclear envelope formation: Mind the gaps. Annu. Rev. Biophys. 38:107–24 [Google Scholar]
  68. Levin R, Grinstein S, Schlam D. 2015. Phosphoinositides in phagocytosis and macropinocytosis. Biochim. Biophys. Acta 1851:805–23 [Google Scholar]
  69. Lim JP, Wang JT, Kerr MC, Teasdale RD, Gleeson PA. 2008. A role for SNX5 in the regulation of macropinocytosis. BMC Cell Biol. 9:58 [Google Scholar]
  70. Ling Y, Hayano S, Novick P. 2014. Osh4p is needed to reduce the level of phosphatidylinositol-4-phosphate on secretory vesicles as they mature. Mol. Biol. Cell 25:3389–400 [Google Scholar]
  71. Liu J, Zuo X, Yue P, Guo W. 2007. Phosphatidylinositol 4,5-bisphosphate mediates the targeting of the exocyst to the plasma membrane for exocytosis in mammalian cells. Mol. Biol. Cell 18:4483–92 [Google Scholar]
  72. Lorente-Rodriguez A, Barlowe C. 2011. Requirement for Golgi-localized PI(4)P in fusion of COPII vesicles with Golgi compartments. Mol. Biol. Cell 22:216–29 [Google Scholar]
  73. Lorenzi R, Brickell PM, Katz DR, Kinnon C, Thrasher AJ. 2000. Wiskott-Aldrich syndrome protein is necessary for efficient IgG-mediated phagocytosis. Blood 95:2943–46 [Google Scholar]
  74. Lu PJ, Shieh WR, Rhee SG, Yin HL, Chen CS. 1996. Lipid products of phosphoinositide 3-kinase bind human profilin with high affinity. Biochemistry 35:14027–34 [Google Scholar]
  75. Lundmark R, Doherty GJ, Howes MT, Cortese K, Vallis Y. et al. 2008. The GTPase-activating protein GRAF1 regulates the CLIC/GEEC endocytic pathway. Curr. Biol. 18:1802–8 [Google Scholar]
  76. Maekawa M, Terasaka S, Mochizuki Y, Kawai K, Ikeda Y. et al. 2014. Sequential breakdown of 3-phosphorylated phosphoinositides is essential for the completion of macropinocytosis. PNAS 111:E978–87 [Google Scholar]
  77. Maffucci T, Brancaccio A, Piccolo E, Stein RC, Falasca M. 2003. Insulin induces phosphatidylinositol-3-phosphate formation through TC10 activation. EMBO J. 22:4178–89 [Google Scholar]
  78. Marshall JG, Booth JW, Stambolic V, Mak T, Balla T. et al. 2001. Restricted accumulation of phosphatidylinositol 3-kinase products in a plasmalemmal subdomain during Fcγ receptor–mediated phagocytosis. J. Cell Biol. 153:1369–80 [Google Scholar]
  79. Martin TF. 2015. PI(4,5)P2-binding effector proteins for vesicle exocytosis. Biochim. Biophys. Acta 1851:785–93 [Google Scholar]
  80. McAlpine F, Williamson LE, Tooze SA, Chan EY. 2013. Regulation of nutrient-sensitive autophagy by uncoordinated 51-like kinases 1 and 2. Autophagy 9:361–73 [Google Scholar]
  81. McMahon HT, Boucrot E. 2011. Molecular mechanism and physiological functions of clathrin-mediated endocytosis. Nat. Rev. Mol. Cell Biol. 12:517–33 [Google Scholar]
  82. Mesmin B, Bigay J, Moser von Filseck J, Lacas-Gervais S, Drin G, Antonny B. 2013. A four-step cycle driven by PI(4)P hydrolysis directs sterol/PI(4)P exchange by the ER-Golgi tether OSBP. Cell 155:830–45 [Google Scholar]
  83. Miki H, Miura K, Takenawa T. 1996. N-WASP, a novel actin-depolymerizing protein, regulates the cortical cytoskeletal rearrangement in a PIP2-dependent manner downstream of tyrosine kinases. EMBO J. 15:5326–35 [Google Scholar]
  84. Mizuno-Yamasaki E, Medkova M, Coleman J, Novick P. 2010. Phosphatidylinositol 4-phosphate controls both membrane recruitment and a regulatory switch of the Rab GEF Sec2p. Dev. Cell 18:828–40 [Google Scholar]
  85. Mizushima N, Levine B, Cuervo AM, Klionsky DJ. 2008. Autophagy fights disease through cellular self-digestion. Nature 451:1069–75 [Google Scholar]
  86. Moser von Filseck J, Copic A, Delfosse V, Vanni S, Jackson CL. et al. 2015. Phosphatidylserine transport by ORP/Osh proteins is driven by phosphatidylinositol 4-phosphate. Science 349:432–36 [Google Scholar]
  87. Murray DH, Tamm LK. 2011. Molecular mechanism of cholesterol- and polyphosphoinositide-mediated syntaxin clustering. Biochemistry 50:9014–22 [Google Scholar]
  88. Nandez R, Balkin DM, Messa M, Liang L, Paradise S. et al. 2014. A role of OCRL in clathrin-coated pit dynamics and uncoating revealed by studies of Lowe syndrome cells. eLife 3:e02975 [Google Scholar]
  89. Obara K, Noda T, Niimi K, Ohsumi Y. 2008. Transport of phosphatidylinositol 3-phosphate into the vacuole via autophagic membranes in Saccharomyces cerevisiae. Genes Cells 13:537–47 [Google Scholar]
  90. Oh P, McIntosh DP, Schnitzer JE. 1998. Dynamin at the neck of caveolae mediates their budding to form transport vesicles by GTP-driven fission from the plasma membrane of endothelium. J. Cell Biol. 141:101–14 [Google Scholar]
  91. Oppelt A, Haugsten EM, Zech T, Danielsen HE, Sveen A. et al. 2014. PIKfyve, MTMR3 and their product PtdIns5P regulate cancer cell migration and invasion through activation of Rac1. Biochem. J. 461:383–90 [Google Scholar]
  92. Oppelt A, Lobert VH, Haglund K, Mackey AM, Rameh LE. et al. 2013. Production of phosphatidylinositol 5-phosphate via PIKfyve and MTMR3 regulates cell migration. EMBO Rep. 14:57–64 [Google Scholar]
  93. Papayannopoulos V, Co C, Prehoda KE, Snapper S, Taunton J, Lim WA. 2005. A polybasic motif allows N-WASP to act as a sensor of PIP2 density. Mol. Cell 17:181–91 [Google Scholar]
  94. Pechstein A, Bacetic J, Vahedi-Faridi A, Gromova K, Sundborger A. et al. 2010. Regulation of synaptic vesicle recycling by complex formation between intersectin 1 and the clathrin adaptor complex AP2. PNAS 107:4206–11 [Google Scholar]
  95. Perez Bay AE, Schreiner R, Mazzoni F, Carvajal-Gonzalez JM, Gravotta D. et al. 2013. The kinesin KIF16B mediates apical transcytosis of transferrin receptor in AP-1B-deficient epithelia. EMBO J. 32:2125–39 [Google Scholar]
  96. Plantard L, Arjonen A, Lock JG, Nurani G, Ivaska J, Stromblad S. 2010. PtdIns(3,4,5)P3 is a regulator of myosin-X localization and filopodia formation. J. Cell Sci. 123:3525–34 [Google Scholar]
  97. Pols MS, Ten BC, Gosavi P, Oorschot V, Klumperman J. 2013. The HOPS proteins hVps41 and hVps39 are required for homotypic and heterotypic late endosome fusion. Traffic 14:219–32 [Google Scholar]
  98. Posor Y, Eichhorn-Gruenig M, Puchkov D, Schoneberg J, Ullrich A. et al. 2013. Spatiotemporal control of endocytosis by phosphatidylinositol-3,4-bisphosphate. Nature 499:233–37 [Google Scholar]
  99. Poteryaev D, Datta S, Ackema K, Zerial M, Spang A. 2010. Identification of the switch in early-to-late endosome transition. Cell 141:497–508 [Google Scholar]
  100. Raiborg C, Bremnes B, Mehlum A, Gillooly DJ, Stang E, Stenmark H. 2001. FYVE and coiled-coil domains determine the specific localisation of Hrs to early endosomes. J. Cell Sci. 114:2255–63 [Google Scholar]
  101. Raiborg C, Schink KO, Stenmark H. 2013. Class III phosphatidylinositol 3-kinase and its catalytic product PtdIns3P in regulation of endocytic membrane traffic. FEBS J. 280:2730–42 [Google Scholar]
  102. Raiborg C, Stenmark H. 2009. The ESCRT machinery in endosomal sorting of ubiquitylated membrane proteins. Nature 458:445–52 [Google Scholar]
  103. Raiborg C, Wenzel EM, Pedersen NM, Olsvik H, Schink KO. et al. 2015. Repeated ER-endosome contacts promote endosome translocation and neurite outgrowth. Nature 520:234–38 [Google Scholar]
  104. Raiborg C, Wenzel EM, Pedersen NM, Stenmark H. 2016. Phosphoinositides in membrane contact sites. Biochem. Soc. Trans. 44:425–30 [Google Scholar]
  105. Rink J, Ghigo E, Kalaidzidis Y, Zerial M. 2005. Rab conversion as a mechanism of progression from early to late endosomes. Cell 122:735–49 [Google Scholar]
  106. Roberts R, Ktistakis NT. 2013. Omegasomes: PI3P platforms that manufacture autophagosomes. Essays Biochem. 55:17–27 [Google Scholar]
  107. Rohde G, Wenzel D, Haucke V. 2002. A phosphatidylinositol (4,5)-bisphosphate binding site within μ2-adaptin regulates clathrin-mediated endocytosis. J. Cell Biol. 158:209–14 [Google Scholar]
  108. Rosivatz E, Woscholski R. 2011. Removal or masking of phosphatidylinositol(4,5)bisphosphate from the outer mitochondrial membrane causes mitochondrial fragmentation. Cell. Signal. 23:478–86 [Google Scholar]
  109. Rossman KL, Der CJ, Sondek J. 2005. GEF means go: turning on RHO GTPases with guanine nucleotide–exchange factors. Nat. Rev. Mol. Cell Biol. 6:167–80 [Google Scholar]
  110. Rusten TE, Vaccari T, Lindmo K, Rodahl LM, Nezis IP. et al. 2007. ESCRTs and Fab1 regulate distinct steps of autophagy. Curr. Biol. 17:1817–25 [Google Scholar]
  111. Sagona AP, Nezis IP, Pedersen NM, Liestol K, Poulton J. et al. 2010. PtdIns(3)P controls cytokinesis through KIF13A-mediated recruitment of FYVE-CENT to the midbody. Nat. Cell Biol. 12:362–71 [Google Scholar]
  112. Saheki Y, De CP. 2012. Synaptic vesicle endocytosis. Cold Spring Harb. Perspect. Biol. 4:a005645 [Google Scholar]
  113. Samie M, Wang X, Zhang X, Goschka A, Li X. et al. 2013. A TRP channel in the lysosome regulates large particle phagocytosis via focal exocytosis. Dev. Cell 26:511–24 [Google Scholar]
  114. Schlam D, Bagshaw RD, Freeman SA, Collins RF, Pawson T. et al. 2015. Phosphoinositide 3-kinase enables phagocytosis of large particles by terminating actin assembly through Rac/Cdc42 GTPase-activating proteins. Nat. Commun. 6:8623 [Google Scholar]
  115. Schmid SL, Frolov VA. 2011. Dynamin: functional design of a membrane fission catalyst. Annu. Rev. Cell Dev. Biol. 27:79–105 [Google Scholar]
  116. Schnatwinkel C, Christoforidis S, Lindsay MR, Uttenweiler-Joseph S, Wilm M. et al. 2004. The Rab5 effector Rabankyrin-5 regulates and coordinates different endocytic mechanisms. PLOS Biol. 2:E261 [Google Scholar]
  117. Sen A, Madhivanan K, Mukherjee D, Aguilar RC. 2012. The epsin protein family: coordinators of endocytosis and signaling. Biomol. Concepts 3:117–26 [Google Scholar]
  118. Shah ZH, Jones DR, Sommer L, Foulger R, Bultsma Y. et al. 2013. Nuclear phosphoinositides and their impact on nuclear functions. FEBS J. 280:6295–310 [Google Scholar]
  119. Shen D, Wang X, Xu H. 2011. Pairing phosphoinositides with calcium ions in endolysosomal dynamics: Phosphoinositides control the direction and specificity of membrane trafficking by regulating the activity of calcium channels in the endolysosomes. BioEssays 33:448–57 [Google Scholar]
  120. Shewan A, Eastburn DJ, Mostov K. 2011. Phosphoinositides in cell architecture. Cold Spring Harb. Perspect. Biol. 3:a004796 [Google Scholar]
  121. Shin HW, Hayashi M, Christoforidis S, Lacas-Gervais S, Hoepfner S. et al. 2005. An enzymatic cascade of Rab5 effectors regulates phosphoinositide turnover in the endocytic pathway. J. Cell Biol. 170:607–18 [Google Scholar]
  122. Shupliakov O, Löw P, Grabs D, Gad H, Chen H. et al. 1997. Synaptic vesicle endocytosis impaired by disruption of dynamin-SH3 domain interactions. Science 276:259–63 [Google Scholar]
  123. Simonsen A, Lippé R, Christoforidis S, Gaullier J-M, Brech A. et al. 1998. EEA1 links PI(3)K function to Rab5 regulation of endosome fusion. Nature 394:494–98 [Google Scholar]
  124. Skruzny M, Brach T, Ciuffa R, Rybina S, Wachsmuth M, Kaksonen M. 2012. Molecular basis for coupling the plasma membrane to the actin cytoskeleton during clathrin-mediated endocytosis. PNAS 109:E2533–42 [Google Scholar]
  125. Slagsvold T, Aasland R, Hirano S, Bache KG, Raiborg C. et al. 2005. Eap45 in mammalian ESCRT-II binds ubiquitin via a phosphoinositide-interacting GLUE domain. J. Biol. Chem. 280:19600–6 [Google Scholar]
  126. Srivastava S, Choudhury P, Li Z, Liu G, Nadkarni V. et al. 2006. Phosphatidylinositol 3-phosphate indirectly activates KCa3.1 via 14 amino acids in the carboxy terminus of KCa3.1. Mol. Biol. Cell 17:146–54 [Google Scholar]
  127. Stalder D, Mizuno-Yamasaki E, Ghassemian M, Novick PJ. 2013. Phosphorylation of the Rab exchange factor Sec2p directs a switch in regulatory binding partners. PNAS 110:19995–20002 [Google Scholar]
  128. Stefan CJ, Manford AG, Baird D, Yamada-Hanff J, Mao Y, Emr SD. 2011. Osh proteins regulate phosphoinositide metabolism at ER–plasma membrane contact sites. Cell 144:389–401 [Google Scholar]
  129. Stenmark H. 2009. Rab GTPases as coordinators of vesicle traffic. Nat. Rev. Mol. Cell Biol. 10:513–25 [Google Scholar]
  130. Stroupe C, Collins KM, Fratti RA, Wickner W. 2006. Purification of active HOPS complex reveals its affinities for phosphoinositides and the SNARE Vam7p. EMBO J. 25:1579–89 [Google Scholar]
  131. Südhof TC, Rothman JE. 2009. Membrane fusion: grappling with SNARE and SM proteins. Science 323:474–77 [Google Scholar]
  132. Suzuki K, Akioka M, Kondo-Kakuta C, Yamamoto H, Ohsumi Y. 2013. Fine mapping of autophagy-related proteins during autophagosome formation in Saccharomyces cerevisiae. J. Cell Sci. 126:2534–44 [Google Scholar]
  133. Swanson JA. 2008. Shaping cups into phagosomes and macropinosomes. Nat. Rev. Mol. Cell Biol. 9:639–49 [Google Scholar]
  134. Teasdale RD, Collins BM. 2012. Insights into the PX (phox-homology) domain and SNX (sorting nexin) protein families: structures, functions and roles in disease. Biochem. J. 441:39–59 [Google Scholar]
  135. Teo H, Gill DJ, Sun J, Perisic O, Veprintsev DB. et al. 2006. ESCRT-I core and ESCRT-II GLUE domain structures reveal central role for GLUE domain in linking to ESCRT-I and membranes. Cell 125:99–111 [Google Scholar]
  136. Tsujita K, Itoh T. 2015. Phosphoinositides in the regulation of actin cortex and cell migration. Biochim. Biophys. Acta 1851:824–31 [Google Scholar]
  137. Ueno T, Falkenburger BH, Pohlmeyer C, Inoue T. 2011. Triggering actin comets versus membrane ruffles: distinctive effects of phosphoinositides on actin reorganization. Sci. Signal. 4:ra87 [Google Scholar]
  138. van Weering JR, Verkade P, Cullen PJ. 2010. SNX-BAR proteins in phosphoinositide-mediated, tubular-based endosomal sorting. Semin. Cell Dev. Biol. 21:371–80 [Google Scholar]
  139. van Weering JR, Verkade P, Cullen PJ. 2012. SNX-BAR-mediated endosome tubulation is co-ordinated with endosome maturation. Traffic 13:94–107 [Google Scholar]
  140. Veltman DM, Lemieux MG, Knecht DA, Insall RH. 2014. PIP3-dependent macropinocytosis is incompatible with chemotaxis. J. Cell Biol. 204:497–505 [Google Scholar]
  141. Viaud J, Lagarrigue F, Ramel D, Allart S, Chicanne G. et al. 2014. Phosphatidylinositol 5-phosphate regulates invasion through binding and activation of Tiam1. Nat. Commun. 5:4080 [Google Scholar]
  142. Vicinanza M, Korolchuk VI, Ashkenazi A, Puri C, Menzies FM. et al. 2015. PI(5)P regulates autophagosome biogenesis. Mol. Cell 57:219–34 [Google Scholar]
  143. von Stein W, Ramrath A, Grimm A, Muller-Borg M, Wodarz A. 2005. Direct association of Bazooka/PAR-3 with the lipid phosphatase PTEN reveals a link between the PAR/aPKC complex and phosphoinositide signaling. Development 132:1675–86 [Google Scholar]
  144. Walch-Solimena C, Collins RN, Novick PJ. 1997. Sec2p mediates nucleotide exchange on Sec4p and is involved in polarized delivery of post-Golgi vesicles. J. Cell Biol. 137:1495–509 [Google Scholar]
  145. Watanabe S, Rost BR, Camacho-Perez M, Davis MW, Sohl-Kielczynski B. et al. 2013. Ultrafast endocytosis at mouse hippocampal synapses. Nature 504:242–47 [Google Scholar]
  146. Weiger MC, Parent CA. 2012. Phosphoinositides in chemotaxis. Subcell. Biochem. 59:217–54 [Google Scholar]
  147. Welch HC, Coadwell WJ, Ellson CD, Ferguson GJ, Andrews SR. et al. 2002. P-Rex1, a PtdIns(3,4,5)P3- and Gβγ-regulated guanine-nucleotide exchange factor for Rac. Cell 108:809–21 [Google Scholar]
  148. Woscholski R. 2014. Chemical intervention tools to probe phosphoinositide-dependent signalling. Biochem. Soc. Trans. 42:1343–48 [Google Scholar]
  149. Wu H, Feng W, Chen J, Chan LN, Huang S, Zhang M. 2007. PDZ domains of Par-3 as potential phosphoinositide signaling integrators. Mol. Cell 28:886–98 [Google Scholar]
  150. Wu Y, Cheng S, Zhao H, Zou W, Yoshina S. et al. 2014. PI3P phosphatase activity is required for autophagosome maturation and autolysosome formation. EMBO Rep. 15:973–81 [Google Scholar]
  151. Wymann MP, Schultz C. 2012. The chemical biology of phosphoinositide 3-kinases. ChemBioChem 13:2022–35 [Google Scholar]
  152. Xu H, Wickner W. 2010. Phosphoinositides function asymmetrically for membrane fusion, promoting tethering and 3Q-SNARE subcomplex assembly. J. Biol. Chem. 285:39359–65 [Google Scholar]
  153. Xue Y, Fares H, Grant B, Li Z, Rose AM. et al. 2003. Genetic analysis of the myotubularin family of phosphatases in Caenorhabditis elegans. J. Biol. Chem. 278:34380–86 [Google Scholar]
  154. Yamashita M, Kurokawa K, Sato Y, Yamagata A, Mimura H. et al. 2010. Structural basis for the Rho- and phosphoinositide-dependent localization of the exocyst subunit Sec3. Nat. Struct. Mol. Biol. 17:180–86 [Google Scholar]
  155. Zhang X, Orlando K, He B, Xi F, Zhang J. et al. 2008. Membrane association and functional regulation of Sec3 by phospholipids and Cdc42. J. Cell Biol. 180:145–58 [Google Scholar]
  156. Zolov SN, Bridges D, Zhang Y, Lee WW, Riehle E. et al. 2012. In vivo, Pikfyve generates PI(3,5)P2, which serves as both a signaling lipid and the major precursor for PI5P. PNAS 109:17472–77 [Google Scholar]
  157. Zoncu R, Perera RM, Balkin DM, Pirruccello M, Toomre D, De CP. 2009. A phosphoinositide switch controls the maturation and signaling properties of APPL endosomes. Cell 136:1110–21 [Google Scholar]

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error