The Lowe Syndrome Protein OCRL1 Is Required for Endocytosis in the Zebrafish Pronephric Tubule

English version České info

Phosphoinositide lipids are key regulators of cellular physiology and consequently enzymes that generate or remove these lipids are of fundamental importance. Mutation of one such enzyme, called OCRL1, causes two disorders in humans, Lowe syndrome and Dent-2 disease. However, the underlying mechanisms remain poorly defined. Here, we demonstrate that OCRL1 regulates endocytosis, the process by which cells internalize material from their extracellular environment. Importantly, this is demonstrated in a physiologically relevant tissue in vivo, namely the zebrafish renal tubule. Defective endocytosis can explain the renal symptoms seen in Lowe syndrome and Dent-2 patients. We also report that defects in cell polarity or cilia formation cannot explain the renal symptoms. This study not only increases our understanding of the endocytic pathway, it also provides a mechanistic explanation for the renal defects observed in Lowe syndrome and Dent-2 patients.

Vyšlo v časopise: The Lowe Syndrome Protein OCRL1 Is Required for Endocytosis in the Zebrafish Pronephric Tubule. PLoS Genet 11(4): e32767. doi:10.1371/journal.pgen.1005058
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005058

Souhrn

Zdroje

1. Nussbaum R, Suchy SF (2001) Lowe syndrome. In: Scriver CR, Beauder AL, Sly WS, Valle D, editors. Metabolic and molecular basis of inherited diseases. New York: McGraw-Hill. pp. 6257–6266.

2. Attree O, Olivos IM, Okabe I, Bailey LC, Nelson DL, et al. (1992) The Lowe's oculocerebrorenal syndrome gene encodes a protein highly homologous to inositol polyphosphate-5-phosphatase. Nature 358: 239–242. 1321346

3. Pirruccello M, De Camilli P (2012) Inositol 5-phosphatases: insights from the Lowe syndrome protein OCRL. Trends Biochem Sci 37: 134–143. doi: 10.1016/j.tibs.2012.01.002 22381590

4. Dressman MA, Olivos-Glander IM, Nussbaum RL, Suchy SF (2000) Ocrl1, a PtdIns(4,5)P(2) 5-phosphatase, is localized to the trans-Golgi network of fibroblasts and epithelial cells. J Histochem Cytochem 48: 179–190. 10639484

5. Ungewickell A, Ward ME, Ungewickell E, Majerus PW (2004) The inositol polyphosphate 5-phosphatase Ocrl associates with endosomes that are partially coated with clathrin. Proc Natl Acad Sci U S A 101: 13501–13506. 15353600

6. Choudhury R, Diao A, Zhang F, Eisenberg E, Saint-Pol A, et al. (2005) Lowe syndrome protein OCRL1 interacts with clathrin and regulates protein trafficking between endosomes and the trans-Golgi network. Mol Biol Cell 16: 3467–3479. 15917292

7. Erdmann KS, Mao Y, McCrea HJ, Zoncu R, Lee S, et al. (2007) A role of the Lowe syndrome protein OCRL in early steps of the endocytic pathway. Dev Cell 13: 377–390. 17765681

8. Vicinanza M, Di Campli A, Polishchuk E, Santoro M, Di Tullio G, et al. (2011) OCRL controls trafficking through early endosomes via PtdIns4,5P(2)-dependent regulation of endosomal actin. EMBO J 30: 4970–4985. doi: 10.1038/emboj.2011.354 21971085

9. Choudhury R, Noakes CJ, McKenzie E, Kox C, Lowe M (2009) Differential clathrin binding and subcellular localization of OCRL1 splice isoforms. J Biol Chem.

10. Grieve AG, Daniels RD, Sanchez-Heras E, Hayes MJ, Moss SE, et al. (2011) Lowe Syndrome Protein OCRL1 Supports Maturation of Polarized Epithelial Cells. PLoS One 6: e24044. doi: 10.1371/journal.pone.0024044 21901156

11. Faucherre A, Desbois P, Nagano F, Satre V, Lunardi J, et al. (2005) Lowe syndrome protein Ocrl1 is translocated to membrane ruffles upon Rac GTPase activation: a new perspective on Lowe syndrome pathophysiology. Hum Mol Genet 14: 1441–1448. 15829501

12. Coon BG, Mukherjee D, Hanna CB, Riese DJ 2nd, Lowe M, et al. (2009) Lowe syndrome patient fibroblasts display Ocrl1-specific cell migration defects that cannot be rescued by the homologous Inpp5b phosphatase. Hum Mol Genet 18: 4478–4491. doi: 10.1093/hmg/ddp407 19700499

13. Bohdanowicz M, Balkin DM, De Camilli P, Grinstein S (2012) Recruitment of OCRL and Inpp5B to phagosomes by Rab5 and APPL1 depletes phosphoinositides and attenuates Akt signaling. Mol Biol Cell 23: 176–187. doi: 10.1091/mbc.E11-06-0489 22072788

14. Marion S, Mazzolini J, Herit F, Bourdoncle P, Kambou-Pene N, et al. (2012) The NF-kappaB signaling protein Bcl10 regulates actin dynamics by controlling AP1 and OCRL-bearing vesicles. Dev Cell 23: 954–967. doi: 10.1016/j.devcel.2012.09.021 23153494

15. Dambournet D, Machicoane M, Chesneau L, Sachse M, Rocancourt M, et al. (2011) Rab35 GTPase and OCRL phosphatase remodel lipids and F-actin for successful cytokinesis. Nat Cell Biol 13: 981–988. doi: 10.1038/ncb2279 21706022

16. Coon BG, Hernandez V, Madhivanan K, Mukherjee D, Hanna CB, et al. (2012) The Lowe syndrome protein OCRL1 is involved in primary cilia assembly. Hum Mol Genet 21: 1835–1847. doi: 10.1093/hmg/ddr615 22228094

17. Luo N, West CC, Murga-Zamalloa CA, Sun L, Anderson RM, et al. (2012) OCRL localizes to the primary cilium: a new role for cilia in Lowe syndrome. Hum Mol Genet 21: 3333–3344. doi: 10.1093/hmg/dds163 22543976

18. Hyvola N, Diao A, McKenzie E, Skippen A, Cockcroft S, et al. (2006) Membrane targeting and activation of the Lowe syndrome protein OCRL1 by rab GTPases. Embo J 25: 3750–3761. 16902405

19. Mao Y, Balkin DM, Zoncu R, Erdmann KS, Tomasini L, et al. (2009) A PH domain within OCRL bridges clathrin-mediated membrane trafficking to phosphoinositide metabolism. Embo J 28: 1831–1842. doi: 10.1038/emboj.2009.155 19536138

20. Swan LE, Tomasini L, Pirruccello M, Lunardi J, De Camilli P (2010) Two closely related endocytic proteins that share a common OCRL-binding motif with APPL1. Proc Natl Acad Sci U S A 107: 3511–3516. doi: 10.1073/pnas.0914658107 20133602

21. Noakes CJ, Lee G, Lowe M (2011) The PH domain proteins IPIP27A and B link OCRL1 to receptor recycling in the endocytic pathway. Mol Biol Cell 22: 606–623. doi: 10.1091/mbc.E10-08-0730 21233288

22. van Rahden VA, Brand K, Najm J, Heeren J, Pfeffer SR, et al. (2012) The 5-phosphatase OCRL mediates retrograde transport of the mannose 6-phosphate receptor by regulating a Rac1-cofilin signalling module. Hum Mol Genet 21: 5019–5038. doi: 10.1093/hmg/dds343 22907655

23. 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: e02975.

24. Ben El Kadhi K, Roubinet C, Solinet S, Emery G, Carreno S (2011) The Inositol 5-Phosphatase dOCRL Controls PI(4,5)P2 Homeostasis and Is Necessary for Cytokinesis. Curr Biol 21: 1074–1079. doi: 10.1016/j.cub.2011.05.030 21658948

25. Rbaibi Y, Cui S, Mo D, Carattino M, Rohatgi R, et al. (2012) OCRL1 modulates cilia length in renal epithelial cells. Traffic 13: 1295–1305. doi: 10.1111/j.1600-0854.2012.01387.x 22680056

26. Suchy SF, Nussbaum RL (2002) The deficiency of PIP2 5-phosphatase in Lowe syndrome affects actin polymerization. Am J Hum Genet 71: 1420–1427. 12428211

27. Bokenkamp A, Ludwig M (2011) Disorders of the renal proximal tubule. Nephron Physiol 118: p1–6. doi: 10.1159/000327892 21778767

28. Norden AG, Lapsley M, Igarashi T, Kelleher CL, Lee PJ, et al. (2002) Urinary megalin deficiency implicates abnormal tubular endocytic function in Fanconi syndrome. J Am Soc Nephrol 13: 125–133. 11752029

29. Janne PA, Suchy SF, Bernard D, MacDonald M, Crawley J, et al. (1998) Functional overlap between murine Inpp5b and Ocrl1 may explain why deficiency of the murine ortholog for OCRL1 does not cause Lowe syndrome in mice. J Clin Invest 101: 2042–2053. 9593760

30. Bothwell SP, Chan E, Bernardini IM, Kuo YM, Gahl WA, et al. (2011) Mouse model for Lowe syndrome/Dent Disease 2 renal tubulopathy. J Am Soc Nephrol 22: 443–448. doi: 10.1681/ASN.2010050565 21183592

31. Ramirez IB, Pietka G, Jones DR, Divecha N, Alia A, et al. (2012) Impaired neural development in a zebrafish model for Lowe syndrome. Hum Mol Genet 21: 1744–1759. doi: 10.1093/hmg/ddr608 22210625

32. Drummond IA, Majumdar A, Hentschel H, Elger M, Solnica-Krezel L, et al. (1998) Early development of the zebrafish pronephros and analysis of mutations affecting pronephric function. Development 125: 4655–4667. 9806915

33. Anzenberger U, Bit-Avragim N, Rohr S, Rudolph F, Dehmel B, et al. (2006) Elucidation of megalin/LRP2-dependent endocytic transport processes in the larval zebrafish pronephros. J Cell Sci 119: 2127–2137. 16638803

34. Vasilyev A, Liu Y, Mudumana S, Mangos S, Lam PY, et al. (2009) Collective cell migration drives morphogenesis of the kidney nephron. PLoS Biol 7: e9. doi: 10.1371/journal.pbio.1000009 19127979

35. Seiler C, Pack M (2010) Transgenic labeling of the zebrafish pronephric duct and tubules using a promoter from the enpep gene. Gene Expr Patterns 11: 118–121. doi: 10.1016/j.gep.2010.10.002 20969977

36. Witzleben CL, Schoen EJ, Tu WH, McDonald LW (1968) Progressive morphologic renal changes in the oculo-cerebro-renal syndrome of Lowe. Am J Med 44: 319–324. 5635681

37. Kaneko K, Hasui M, Hata A, Hata D, Nozu K (2010) Focal segmental glomerulosclerosis in a boy with Dent-2 disease. Pediatr Nephrol 25: 781–782. doi: 10.1007/s00467-009-1362-z 19902262

38. Piwon N, Gunther W, Schwake M, Bosl MR, Jentsch TJ (2000) ClC-5 Cl—channel disruption impairs endocytosis in a mouse model for Dent's disease. Nature 408: 369–373. 11099045

39. Christensen EI, Devuyst O, Dom G, Nielsen R, Van der Smissen P, et al. (2003) Loss of chloride channel ClC-5 impairs endocytosis by defective trafficking of megalin and cubilin in kidney proximal tubules. Proc Natl Acad Sci U S A 100: 8472–8477. 12815097

40. Leheste JR, Rolinski B, Vorum H, Hilpert J, Nykjaer A, et al. (1999) Megalin knockout mice as an animal model of low molecular weight proteinuria. Am J Pathol 155: 1361–1370. 10514418

41. Kur E, Christa A, Veth KN, Gajera CR, Andrade-Navarro MA, et al. (2011) Loss of Lrp2 in zebrafish disrupts pronephric tubular clearance but not forebrain development. Dev Dyn 240: 1567–1577. doi: 10.1002/dvdy.22624 21455927

42. Hatae T, Fujita M, Sagara H, Okuyama K (1986) Formation of apical tubules from large endocytic vacuoles in kidney proximal tubule cells during absorption of horseradish peroxidase. Cell Tissue Res 246: 271–278. 3779809

43. Birn H, Christensen EI, Nielsen S (1993) Kinetics of endocytosis in renal proximal tubule studied with ruthenium red as membrane marker. Am J Physiol 264: F239–250. 7680532

44. Raghavan V, Rbaibi Y, Pastor-Soler NM, Carattino MD, Weisz OA (2014) Shear stress-dependent regulation of apical endocytosis in renal proximal tubule cells mediated by primary cilia. Proc Natl Acad Sci U S A 111: 8506–8511. doi: 10.1073/pnas.1402195111 24912170

45. Kramer-Zucker AG, Olale F, Haycraft CJ, Yoder BK, Schier AF, et al. (2005) Cilia-driven fluid flow in the zebrafish pronephros, brain and Kupffer's vesicle is required for normal organogenesis. Development 132: 1907–1921. 15790966

46. Liu Y, Pathak N, Kramer-Zucker A, Drummond IA (2007) Notch signaling controls the differentiation of transporting epithelia and multiciliated cells in the zebrafish pronephros. Development 134: 1111–1122. 17287248

47. Pirruccello M, Swan LE, Folta-Stogniew E, De Camilli P (2011) Recognition of the F&H motif by the Lowe syndrome protein OCRL. Nat Struct Mol Biol 18: 789–795. doi: 10.1038/nsmb.2071 21666675

48. Hou X, Hagemann N, Schoebel S, Blankenfeldt W, Goody RS, et al. (2011) A structural basis for Lowe syndrome caused by mutations in the Rab-binding domain of OCRL1. EMBO J 30: 1659–1670. doi: 10.1038/emboj.2011.60 21378754

49. McCrea HJ, Paradise S, Tomasini L, Addis M, Melis MA, et al. (2008) All known patient mutations in the ASH-RhoGAP domains of OCRL affect targeting and APPL1 binding. Biochem Biophys Res Commun 369: 493–499. doi: 10.1016/j.bbrc.2008.02.067 18307981

50. Hichri H, Rendu J, Monnier N, Coutton C, Dorseuil O, et al. (2011) From Lowe syndrome to Dent disease: correlations between mutations of the OCRL1 gene and clinical and biochemical phenotypes. Hum Mutat 32: 379–388. doi: 10.1002/humu.21391 21031565

51. Cui S, Guerriero CJ, Szalinski CM, Kinlough CL, Hughey RP, et al. (2010) OCRL1 function in renal epithelial membrane traffic. Am J Physiol Renal Physiol 298: F335–345. doi: 10.1152/ajprenal.00453.2009 19940034

52. Wu G, Zhang W, Na T, Jing H, Wu H, et al. (2012) Suppression of intestinal calcium entry channel TRPV6 by OCRL, a lipid phosphatase associated with Lowe syndrome and Dent disease. Am J Physiol Cell Physiol 302: C1479–1491. doi: 10.1152/ajpcell.00277.2011 22378746

53. Zeigerer A, Gilleron J, Bogorad RL, Marsico G, Nonaka H, et al. (2012) Rab5 is necessary for the biogenesis of the endolysosomal system in vivo. Nature 485: 465–470. doi: 10.1038/nature11133 22622570

54. Lin Z, Jin S, Duan X, Wang T, Martini S, et al. (2011) Chloride channel (Clc)-5 is necessary for exocytic trafficking of Na+/H+ exchanger 3 (NHE3). J Biol Chem 286: 22833–22845. doi: 10.1074/jbc.M111.224998 21561868

55. Waters AM, Beales PL (2011) Ciliopathies: an expanding disease spectrum. Pediatr Nephrol 26: 1039–1056. doi: 10.1007/s00467-010-1731-7 21210154

56. Conduit SE, Dyson JM, Mitchell CA (2012) Inositol polyphosphate 5-phosphatases; new players in the regulation of cilia and ciliopathies. FEBS Lett 586: 2846–2857. doi: 10.1016/j.febslet.2012.07.037 22828281

57. Mak LH, Georgiades SN, Rosivatz E, Whyte GF, Mirabelli M, et al. (2011) A small molecule mimicking a phosphatidylinositol (4,5)-bisphosphate binding pleckstrin homology domain. ACS Chem Biol 6: 1382–1390. doi: 10.1021/cb2003187 21958214

58. Clark BS, Winter M, Cohen AR, Link BA (2011) Generation of Rab-based transgenic lines for in vivo studies of endosome biology in zebrafish. Dev Dyn 240: 2452–2465. doi: 10.1002/dvdy.22758 21976318

59. Williams ME, Wilke SA, Daggett A, Davis E, Otto S, et al. (2011) Cadherin-9 regulates synapse-specific differentiation in the developing hippocampus. Neuron 71: 640–655. doi: 10.1016/j.neuron.2011.06.019 21867881

60. Kremer JR, Mastronarde DN, McIntosh JR (1996) Computer visualization of three-dimensional image data using IMOD. J Struct Biol 116: 71–76. 8742726

61. Jones DR, Ramirez IB, Lowe M, Divecha N (2013) Measurement of phosphoinositides in the zebrafish Danio rerio. Nat Protoc 8: 1058–1072. doi: 10.1038/nprot.2013.040 23660755