Krebs medal review: PtdIns3P in tumour suppression 25 Xu YHH, Seet L, Wong SH & Hong W (2001) Sorting nexin 3 (SNX3) regulates endosomal function via its PX domain-mediated interaction with phosphatidylinositol 3-phosphate. Nature Cell Biol 3, 658–666. 26 Kanai F, Liu H, Akbary H, Field S, Matsuo T, Brown G, Cantley LC & Yaffe MB (2001) The PX domains of p47phox and p40phox bind to lipid products of phos- phoinositide 3-kinase. Nature Cell Biol 3, 675–678. 27 Cheever ML, Sato TK, de Beer T, Kutateladze T, Emr SD & Overduin M (2001) Phox domain interaction with PtdIns(3)P targets Vam7 t-SNARE to vacuole mem- branes. Nature Cell Biol 3, 613–618. 28 Lemmon MA (2008) Membrane recognition by phos- pholipid-binding domains. Nat Rev Mol Cell Biol 9, 99–111. 29 Birkeland HC & Stenmark H (2004) Protein targeting to endosomes and phagosomes via FYVE and PX domains. Curr Top Microbiol Immunol 282, 89–115. 30 Proikas-Cezanne T, Waddell S, Gaugel A, Frickey T, Lupas A & Nordheim A (2004) WIPI-1alpha (WIPI49), a member of the novel 7-bladed WIPI protein family, is aberrantly expressed in human cancer and is linked to starvation-induced autophagy. Oncogene 23, 9314–9325. 31 Dove SK, Piper RC, McEwen RK, Yu JW, King MC, Hughes DC, Thuring J, Holmes AB, Cooke FT, Mic- hell RH et al. (2004) Svp1p deﬁnes a family of phos- phatidylinositol 3,5-bisphosphate effectors. EMBO J 23, 1922–1933. 32 Slagsvold T, Aasland R, Hirano S, Bache KG, Raiborg C, Trambaiolo D, Wakatsuki S & Stenmark H (2005) Eap45 in mammalian ESCRT-II binds ubiquitin via a phosphoinositide-interacting GLUE domain. J Biol Chem 280, 19600–19606. 33 Hirano S, Suzuki N, Slagsvold T, Kawasaki M, Trambaiolo D, Kato R, Stenmark H & Wakatsuki S (2006) Structural basis of ubiquitin recognition by mammalian Eap45 GLUE domain. Nat Struct Mol Biol 13, 1031–1032. 34 Teo H, Gill DJ, Sun J, Perisic O, Veprintsev DB, Vallis Y, Emr SD & Williams RL (2006) ESCRT-I core and ESCRT-II GLUE domain structures reveal central role for GLUE domain in linking to ESCRT-I and mem- branes. Cell 125, 99–111. 35 Gillooly DJ, Morrow IC, Lindsay M, Gould R, Bryant NJ, Gaullier J-M, Parton RG & Stenmark H (2000) Localization of phosphatidylinositol 3-phosphate in yeast and mammalian cells. EMBO J 19, 4577–4588. 36 Hayakawa A, Hayes SJ, Lawe DC, Sudharshan E, Tuft R, Fogarty K, Lambright D & Corvera S (2004) Structural basis for endosomal targeting by FYVE domains. J Biol Chem 279, 5958–5966. 37 Scott CC, Cuellar-Mata P, Matsuo T, Davidson HW & Grinstein S (2002) Role of 3-phosphoinositides in the maturation of Salmonella-containing vacuoles within host cells. J Biol Chem 277, 12770–12776. H. Stenmark 38 Maffucci T, Brancaccio A, Piccolo E, Stein RC & Fala- sca M (2003) Insulin induces phosphatidylinositol-3- phosphate formation through TC10 activation. EMBO J 22, 4178–4189. 39 Maffucci T, Cooke FT, Foster FM, Traer CJ, Fry MJ & Falasca M (2005) Class II phosphoinositide 3-kinase deﬁnes a novel signaling pathway in cell migration. J Cell Biol 169, 789–799. 40 Vanhaesebroeck B, Guillermet-Guibert J, Graupera M & Bilanges B (2010) The emerging mechanisms of iso- form-speciﬁc PI3K signalling. Nat Rev Mol Cell Biol 11 329–341. 41 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, 537–547. 42 Axe EL, Walker SA, Manifava M, Chandra P, Roderick HL, Habermann A, Grifﬁths G & Ktistakis NT (2008) Autophagosome formation from compart- ments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum. J Cell Biol 182, 685–701. 43 Herman PK, Stack JH, DeModena JA & Emr SD (1991) A novel protein kinase homolog essential for protein sorting to the yeast lysosome-like vacuole. Cell 64, 425–437. 44 Burd CG, Peterson M, Cowles CR & Emr SD (1997) A novel Sec18p ⁄ NSF-dependent complex required for Golgi-to- endosome transport in yeast. Mol Biol Cell 8, 1089–1104. 45 Tall GG, Hama H, DeWald DB & Horazdovsky BF (1999) The phosphatidylinositol 3-phosphate binding protein Vac1p interacts with a Rab GTPase and a Sec1p homologue to facilitate vesicle-mediated vacuolar protein sorting. Mol Biol Cell 10, 1873–1889. 46 Nielsen E, Christoforidis S, Uttenweiler-Joseph S, Mia- czynska M, Dewitte F, Wilm M, Hoﬂack B & Zerial M (2000) Rabenosyn-5, a novel Rab5 effector, is complexed with hVPS45 and recruited to endosomes through a FYVE ﬁnger domain. J Cell Biol 151, 601–612. 47 Morrison HA, Dionne H, Rusten TE, Brech A, Fisher WW, Pfeiffer BD, Celniker SE, Stenmark H & Bilder D (2008) Regulation of early endosomal entry by the Dro- sophila tumor suppressors Rabenosyn and Vps45. Mol Biol Cell 19, 4167–4176. 48 Mottola G, Classen AK, Gonzalez-Gaitan M, Eaton S & Zerial M (2010) A novel function for the Rab5 effec- tor Rabenosyn-5 in planar cell polarity. Development 137, 2353–2364. 49 Wang Y (2009) Wnt ⁄ Planar cell polarity signaling: a new paradigm for cancer therapy. Mol Cancer Ther 8, 2103–2109. 50 Simonsen A, Lippe´ R, Christoforidis S, Gaullier J-M, Brech A, Callaghan J, Toh B-H, Murphy C, Zerial M & Stenmark H (1998) EEA1 links PI(3)K function to 4846 FEBS Journal 277 (2010) 4837–4848 ª 2010 The Author Journal compilation ª 2010 FEBS