Loss of PIKfyve in platelets causes a lysosomal disease leading to inflammation and thrombosis in mice

Nature Communications

Volumn 5, Issue , 2014, Pages

  Min, Sang H ^a   Suzuki, Aae ^a   Stalker, Timothy J ^a   Zhao, Liang ^a   Wang, Yuhuan ^b   McKennan, Chris ^b   Riese, Matthew J ^a   Guzman, Jessica F ^a   Zhang, Suhong ^a   Lian, Lurong ^a   Joshi, Rohan ^a   Meng, Ronghua ^a   Seeholzer, Steven H ^b   Choi, John K ^c   Koretzky, Gary ^a   Marks, Michael S ^a   Abrams, Charles S ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b Childrens Hospital of Philadelphia   (United States)

^c ST JUDE CHILDREN S RESEARCH HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CATHEPSIN B; CATHEPSIN D; CRE RECOMBINASE; HEMOGLOBIN; LYSOSOME ENZYME; PHOSPHOTRANSFERASE; PIKFYVE PROTEIN; UNCLASSIFIED DRUG; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,5-DIPHOSPHATE; PIKFYVE PROTEIN, MOUSE; POLYPHOSPHOINOSITIDE;

DISEASE INCIDENCE; MATURATION; MEMBRANE; RODENT; SECRETION;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTERY THROMBOSIS; ARTICLE; BODY FAT; BONE DENSITY; CAROTID ARTERY; CONTROLLED STUDY; CYTOPLASM; DUAL ENERGY X RAY ABSORPTIOMETRY; ENZYME RELEASE; EXON; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HEMOGLOBIN BLOOD LEVEL; IMMUNOBLOTTING; INFLAMMATION; INTRACELLULAR SIGNALING; LEAN BODY WEIGHT; LIQUID CHROMATOGRAPHY; LOXP SITE; LYSOSOME; LYSOSOME DISEASE; MACROPHAGE; MEGAKARYOCYTE; MEGAKARYOPOIESIS; MELANOSOME; MONONUCLEAR CELL; MOUSE; NONHUMAN; PATHOGENESIS; PHYSICAL DISEASE BY ETIOLOGY AND PATHOGENESIS; TANDEM MASS SPECTROMETRY; THROMBOCYTE; THROMBOCYTE ACTIVATION; THROMBOCYTOPENIA; THROMBOCYTOPOIESIS; TRANSMISSION ELECTRON MICROSCOPY; ANIMAL; BODY WEIGHT; C57BL MOUSE; CELL GRANULE; COMPLICATION; DEFICIENCY; ENDOSOME; ENZYMOLOGY; GENE EXPRESSION REGULATION; GENETICS; INFERTILITY; KNOCKOUT MOUSE; LONGEVITY; LYSOSOME STORAGE DISEASE; METABOLISM; PATHOLOGY; SIGNAL TRANSDUCTION; THROMBOCYTE COUNT; THROMBOSIS;

ANIMALS; BLOOD PLATELETS; BODY WEIGHT; CYTOPLASMIC GRANULES; ENDOSOMES; GENE EXPRESSION REGULATION; INFERTILITY; INFLAMMATION; LONGEVITY; LYSOSOMAL STORAGE DISEASES; LYSOSOMES; MACROPHAGES; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; PHOSPHATIDYLINOSITOL 3-KINASES; PHOSPHATIDYLINOSITOL PHOSPHATES; PLATELET COUNT; SIGNAL TRANSDUCTION; THROMBOSIS;

EID: 84907339485     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms5691     Document Type: Article

References (59)

1. Di Paolo, G. & De Camilli, P. Phosphoinositides in cell regulation and membrane dynamics. Nature 443, 651-657 (2006).
2. McCrea, H. J. & De Camilli, P. Mutations in phosphoinositide metabolizing enzymes and human disease. Physiology 24, 8-16 (2009).
3. Shisheva, A. PIKfyve: partners, significance, debates and paradoxes. Cell Biol. Int. 32, 591-604 (2008).
4. Gary, J. D. et al. Regulation of Fab1 phosphatidylinositol 3-phosphate 5-kinase pathway by Vac7 protein and Fig4, a polyphosphoinositide phosphatase family member. Mol. Biol. Cell 13, 1238-1251 (2002).
5. Sbrissa, D. et al. Core protein machinery for mammalian phosphatidylinositol 3,5-bisphosphate synthesis and turnover that regulates the progression of endosomal transport. Novel Sac phosphatase joins the ArPIKfyve-PIKfyve complex. J. Biol. Chem. 282, 23878-23891 (2007).
6. Jin, N. et al. VAC14 nucleates a protein complex essential for the acute interconversion of PI3P and PI(3,5)P(2) in yeast and mouse. EMBO J. 27, 3221-3234 (2008).
7. Sbrissa, D., Ikonomov, O. C., Fenner, H. & Shisheva, A. ArPIKfyve homomeric and heteromeric interactions scaffold PIKfyve and Sac3 in a complex to promote PIKfyve activity and functionality. J. Mol. Biol. 384, 766-779 (2008).
8. Dove, S. K., Dong, K., Kobayashi, T., Williams, F. K. & Michell, R. H. Phosphatidylinositol 3,5-bisphosphate and Fab1p/PIKfyve underPPIn endo-lysosome function. Biochem. J. 419, 1-13 (2009).
9. McCartney, A. J., Zhang, Y. & Weisman, L. S. Phosphatidylinositol 3,5-bisphosphate: low abundance, high significance. BioEssays 36, 52-64 (2014).
10. Takasuga, S. & Sasaki, T. Phosphatidylinositol-3,5-bisphosphate: metabolism and physiological functions. J. Biochem. 154, 211-218 (2013).
11. Ikonomov, O. C. et al. The phosphoinositide kinase PIKfyve is vital in early embryonic development: preimplantation lethality of PIKfyve-/- embryos but normality of PIKfyve + /- mice. J. Biol. Chem. 286, 13404-13413 (2011).
12. Zolov, S. N. et al. In vivo, Pikfyve generates PI(3,5)P2, which serves as both a signaling lipid and the major precursor for PI5P. Proc. Natl Acad. Sci. USA 109, 17472-17477 (2012).
13. Zhang, Y. et al. Loss of Vac14, a regulator of the signaling lipid phosphatidylinositol 3,5-bisphosphate, results in neurodegeneration in mice. Proc. Natl Acad. Sci. USA 104, 17518-17523 (2007).
14. Chow, C. Y. et al. Mutation of FIG4 causes neurodegeneration in the pale tremor mouse and patients with CMT4J. Nature 448, 68-72 (2007).
15. Chow, C. Y. et al. Deleterious variants of FIG4, a phosphoinositide phosphatase, in patients with ALS. Am. J. Hum. Genet. 84, 85-88 (2009).
16. Min, S. H. & Abrams, C. S. Regulation of platelet plug formation by phosphoinositide metabolism. Blood 122, 1358-1365 (2013).
17. King, S. M. & Reed, G. L. Development of platelet secretory granules. Semin. Cell Dev. Biol. 13, 293-302 (2002).
18. Whiteheart, S. W. Platelet granules: surprise packages. Blood 118, 1190-1191 (2011).
19. Heijnen, H. F. et al. Multivesicular bodies are an intermediate stage in the formation of platelet alpha-granules. Blood 91, 2313-2325 (1998).
20. Youssefian, T. & Cramer, E. M. Megakaryocyte dense granule components are sorted in multivesicular bodies. Blood 95, 4004-4007 (2000).
21. Ambrosio, A. L., Boyle, J. A. & Di Pietro, S. M. Mechanism of platelet dense granule biogenesis: study of cargo transport and function of Rab32 and Rab38 in a model system. Blood 120, 4072-4081 (2012).
22. Meng, R. et al. SLC35D3 delivery from megakaryocyte early endosomes is required for platelet dense granule biogenesis and is differentially defective in Hermansky-Pudlak syndrome models. Blood 120, 404-414 (2012).
23. Tiedt, R., Schomber, T., Hao-Shen, H. & Skoda, R. C. Pf4-Cre transgenic mice allow the generation of lineage-restricted gene knockouts for studying megakaryocyte and platelet function in vivo. Blood 109, 1503-1506 (2007).
24. Bertozzi, C. C. et al. Platelets regulate lymphatic vascular development through CLEC-2-SLP-76 signaling. Blood 116, 661-670 (2010).
25. Carramolino, L. et al. Platelets play an essential role in separating the blood and lymphatic vasculatures during embryonic angiogenesis. Circ. Res. 106, 1197-1201 (2010).
26. Josefsson, E. C. et al. Megakaryocytes possess a functional intrinsic apoptosis pathway that must be restrained to survive and produce platelets. J. Exp. Med. 208, 2017-2031 (2011).
27. Soriano, P. Generalized lacZ expression with the ROSA26 Cre reporter strain. Nat. Genet. 21, 70-71 (1999).
28. Nieswandt, B., Bergmeier, W., Rackebrandt, K., Gessner, J. E. & Zirngibl, H. Identification of critical antigen-specific mechanisms in the development of immune thrombocytopenic purpura in mice. Blood 96, 2520-2527 (2000).
29. Bergmeier, W., Rackebrandt, K., Schroder, W., Zirngibl, H. & Nieswandt, B. Structural and functional characterization of the mouse von Willebrand factor receptor GPIb-IX with novel monoclonal antibodies. Blood 95, 886-893 (2000).
30. Trowbridge, E. A. & Martin, J. F. An analysis of the platelet and polyploid megakaryocyte response to acute thrombocytopenia and its biological implications. Clin. Phys. Physiol. Meas. 5, 263-277 (1984).
31. Bentfeld-Barker, M. E. & Bainton, D. F. Identification of primary lysosomes in human megakaryocytes and platelets. Blood 59, 472-481 (1982).
32. Rendu, F. et al. Signal transduction in normal and pathological thrombinstimulated human platelets. Biochimie 69, 305-313 (1987).
33. Lip, G. Y. & Blann, A. von Willebrand factor: a marker of endothelial dysfunction in vascular disorders? Cardiovasc. Res. 34, 255-265 (1997).
34. Cullinane, A. R. et al. A BLOC-1 mutation screen reveals that PLDN is mutated in Hermansky-Pudlak Syndrome type 9. Am. J. Hum. Genet. 88, 778-787 (2011).
35. Wei, A. H. & Li, W. Hermansky-Pudlak syndrome: pigmentary and nonpigmentary defects and their pathogenesis. Pigment Cell Melanoma Res. 26, 176-192 (2013).
36. Marks, M. S., Heijnen, H. F. & Raposo, G. Lysosome-related organelles: unusual compartments become mainstream. Curr. Opin. Cell Biol. 25, 495-505 (2013).
37. Novak, E. K., Hui, S. W. & Swank, R. T. Platelet storage pool deficiency in mouse pigment mutations associated with seven distinct genetic loci. Blood 63, 536-544 (1984).
38. Kornfeld, S. Trafficking of lysosomal enzymes. FASEB J. 1, 462-468 (1987).
39. Rutherford, A. C. et al. The mammalian phosphatidylinositol 3-phosphate 5-kinase (PIKfyve) regulates endosome-to-TGN retrograde transport. J. Cell Sci. 119, 3944-3957 (2006).
40. Benes, P., Vetvicka, V. & Fusek, M. Cathepsin D-many functions of one aspartic protease. Crit. Rev. Oncol. Hematol. 68, 12-28 (2008).
41. Sardiello, M. et al. A gene network regulating lysosomal biogenesis and function. Science 325, 473-477 (2009).
42. Settembre, C., Fraldi, A., Medina, D. L. & Ballabio, A. Signals from the lysosome: a control centre for cellular clearance and energy metabolism. Nat. Rev. 14, 283-296 (2013).
43. Vetvicka, V., Vashishta, A., Saraswat-Ohri, S. & Vetvickova, J. Procathepsin D and cancer: from molecular biology to clinical applications. World J. Clin. Oncol. 1, 35-40 (2010).
44. Mathieu, M., Vignon, F., Capony, F. & Rochefort, H. Estradiol down-regulates the mannose-6-phosphate/insulin-like growth factor-II receptor gene and induces cathepsin-D in breast cancer cells: a receptor saturation mechanism to increase the secretion of lysosomal proenzymes. Mol. Endocrinol. 5, 815-822 (1991).
45. Isidoro, C., Baccino, F. M. & Hasilik, A. Mis-sorting of procathepsin D in metastogenic tumor cells is not due to impaired synthesis of the phosphomannosyl signal. Int. J. Cancer 70, 561-566 (1997).
46. Platt, F. M., Boland, B. & van der Spoel, A. C. The cell biology of disease: lysosomal storage disorders: the cellular impact of lysosomal dysfunction. J. Cell Biol. 199, 723-734 (2012).
47. Vogel, P. et al. Comparative pathology of murine mucolipidosis types II and IIIC. Vet. Pathol. 46, 313-324 (2009).
48. Zhang, X. et al. Mutation of FIG4 causes a rapidly progressive, asymmetric neuronal degeneration. Brain 131, 1990-2001 (2008).
49. Vitner, E. B., Platt, F. M. & Futerman, A. H. Common and uncommon pathogenic cascades in lysosomal storage diseases. J. Biol. Chem. 285, 20423-20427 (2010).
50. Boven, L. A. et al. Gaucher cells demonstrate a distinct macrophage phenotype and resemble alternatively activated macrophages. Am. J. Clin. Pathol. 122, 359-369 (2004).
51. Parkinson-Lawrence, E. J. et al. Lysosomal storage disease: revealing lysosomal function and physiology. Physiology 25, 102-115 (2010).
52. Winters, J. J. et al. Congenital CNS hypomyelination in the Fig4 null mouse is rescued by neuronal expression of the PI(3,5)P(2) phosphatase Fig4. J. Neurosci. 31, 17736-17751 (2011).
53. Bentfeld, M. E. & Bainton, D. F. Cytochemical localization of lysosomal enzymes in rat megakaryocytes and platelets. J. Clin. Invest. 56, 1635-1649 (1975).
54. Ciferri, S. et al. Platelets release their lysosomal content in vivo in humans upon activation. Thromb. Haemost. 83, 157-164 (2000).
55. Rendu, F. & Brohard-Bohn, B. The platelet release reaction: granules' constituents, secretion and functions. Platelets 12, 261-273 (2001).
56. Muir, E. M. & Bowyer, D. E. Inhibition of pinocytosis and induction of release of lysosomal contents by lysosomal overload of arterial smooth muscle cells in vitro. Atherosclerosis 50, 85-92 (1984).
57. Holmsen, H. & Dangelmaier, C. A. Measurement of secretion of lysosomal acid glycosidases. Methods Enzymol. 169, 336-342 (1989).
58. Yasuda, Y. et al. Characterization of new fluorogenic substrates for the rapid and sensitive assay of cathepsin E and cathepsin D. J. Biochem. 125, 1137-1143 (1999).
59. Choi, H., Fermin, D. & Nesvizhskii, A. I. Significance analysis of spectral count data in label-free shotgun proteomics. Mol. Cell. Proteomics 7, 2373-2385 (2008).