Phosphatidylinositol 5-phosphate

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Phosphatidylinositol 5-phosphate (PtdIns5P) is a phosphoinositide, one of the phosphorylated derivatives of phosphatidylinositol (PtdIns), that are well-established membrane-anchored regulatory molecules. Phosphoinositides participate in signaling events that control cytoskeletal dynamics, intracellular membrane trafficking, cell proliferation and many other cellular functions. Generally, phosphoinositides transduce signals by recruiting specific phosphoinositide-binding proteins to intracellular membranes. [1]

Contents

Phosphatidylinositol 5-phosphate is one of the 7 known cellular phosphoinositides with less understood functions. It is phosphorylated on position D-5 of the inositol head group, which is attached via phosphodiester linkage to diacylglycerol (with varying chemical composition of the acyl chains, frequently 1-stearoyl-2-arachidonoyl chain). In quiescent cells, on average, PtdIns5P is of similar or higher abundance as compared to PtdIns3P and ~20-100-fold below the levels of PtdIns4P (Phosphatidylinositol 4-phosphate and PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate). [2] Notably, steady-state PtdIns5P levels are more than 5-fold higher than those of PtdIns(3,5)P2. [3] [4]

PtdIns5P was first demonstrated by HPLC (high pressure liquid chromatography) in mouse fibroblasts as a substrate for PtdIns(4,5)P2 synthesis by type II PIP kinases (1-phosphatidylinositol-5-phosphate 4-kinase). [5] In many cell types, however, PtdIns5P is not detected by HPLC due to technical limitations associated with its poor separation from the abundant PtdIns4P. [6] Rather, PtdIns5P is measured by the "mass assay", where PtdIns5P (as a part of the extracted cellular lipids) is converted in vitro by purified PtdIns5P 4-kinase to PtdIns(4,5)P2 that is subsequently quantified. [7]

Based on studies with the mass assay [6] and an improved HPLC technique, [8] PtdIns5P is detected in all studied mammalian cells. Most of the cellular PtdIns5P is found on cytoplasmic membranes whereas a smaller fraction resides in the nucleus. [9] The cytoplasmic and nuclear pools have distinct functions and regulation. [10]

Metabolism

Cellular PtdIns5P could be produced by D-5-phosphorylation of phosphatidylinositol or by dephosphorylation of PtdIns(3,5)P2 or PtdIns(4,5)P2. Each of these possibilities is experimentally supported. PtdIns5P is synthesized in vitro by PIKfyve, an enzyme principally responsible for PtdIns(3,5)P2 production, [11] [12] as well as by [PIP5K]s. [13] A major role for PIKfyve in synthesis of cellular PtdIns5P is suggested by data for reduced PtdIns5P mass levels upon heterologous overexpression of the enzymatically inactive PIKfyve point-mutant (PIKfyveK1831E) [6] [14] and PIKfyve silencing by small interfering RNAs. [15] Such a role is reinforced by data in transgenic fibroblasts with one genetically disrupted PIKfyve allele, demonstrating equal reduction of steady-state levels of PtdIns5P and PtdIns(3,5)P2. [3]

Likewise, similar reduction of PtdIns5P and PtdIns(3,5)P2 is found in fibroblasts with knockout of the PIKfyve activator [16] ArPIKfyve/VAC14. [4] This experimental evidence coupled with the fact that the cellular levels of PtdIns5P exceed more than 5-fold those of PtdIns(3,5)P2 indicate a predominant role of PIKfyve in maintenance of the steady-state PtdIns5P levels via D-5 phosphorylation of phosphatidylinositol.

A role for the myotubularin protein family in PtdIns5P production has been proposed based on dephosphorylation of PtdIns(3,5)P2 by overexpressed myotubularin 1. [17] Concordantly, genetic ablation of the myotubularin-related protein 2 (MTMR2) causes elevation of cellular PtdIns(3,5)P2 and a decrease of PtdIns5P. [18] The low cellular levels of PtdIns(3,5)P2 suggest that myotubularin phosphatase activity plays a minor role in maintaining the steady-state PtdIns5P levels. Importantly, PtdIns(3,5)P2 is synthesized from PtdIns3P by the PIKfyve complex that includes ArPIKfyve and Sac3/Fig4. [19] Noteworthy, the PIKfyve complex underlies both PtdIns(3,5)P2 synthesis from and turnover to PtdIns3P. [20] The relative proportion of PtdIns(3,5)P2 turnover by myotubularin phosphatases versus that by Sac3 is unknown.

PtdIns5P can also be produced by dephosphorylation of PtdIns(4,5)P2. Such phosphatase activity is shown for Shigella flexneri effector IpgD [21] and two mammalian phosphatases – PtdIns(4,5)P2 4-phosphatase type I and type II. [22]

Currently, there is no known mammalian phosphatase to specifically dephosphorylate PtdIns5P. The pathway for PtdIns5P clearance involves synthesis of PtdIns(4,5)P2. [10]

Functions

The levels of PtdIns5P change significantly in response to physiological and pathological stimuli. Insulin, [8] [23] thrombin, [7] T-cell activation, [24] and cell transformation with nucleophosmin anaplastic lymphoma tyrosine kinase (NPM-ALK), [15] cause elevation of cellular PtdIns5P levels. In contrast, hypoosmotic shock [6] and histamine treatment [25] decrease the levels of PtdIns5P. In T-cells, two “downstream of tyrosine kinase” proteins DOK1 and DOK2 are proposed as PtdIns5P-binding proteins and effectors. [24]

As the other phosphoinositides, PtdIns5P is also present in the nucleus of mammalian cells. [26] The nuclear PtdIns5P pool is controlled by the nuclear type I PtdIns(4,5)P2 4-phosphatase that, in conjunction with the PIPKIIbeta kinase, plays a role in UV stress, apoptosis and cell cycle progression. [9] [27] [28]

The function of PtdIns5P in nuclear signaling likely involves ING2, a member of the ING family. The proteins of this family associate with and modulate the activity of histone acetylases and deacetylases as well as induce apoptosis through p53 acetylation. The ING2 interacts with PtdIns5P via its plant homeodomain (PHD) finger motif. [29]

In summary, the available evidence indicates that PIKfyve activity is the major source of steady-state cellular PtdIns5P. Under certain conditions, PtdIns5P is produced by dephosphorylation of bis-phosphoinositides. PtdIns5P is involved in regulation of both basic cellular functions and responses to a multitude of physiological and pathological stimuli by yet- to- be specified molecular mechanisms.

Related Research Articles

<span class="mw-page-title-main">Phosphatidylinositol</span> Signaling molecule

Phosphatidylinositol or inositol phospholipid is a biomolecule. It was initially called "inosite" when it was discovered by Léon Maquenne and Johann Joseph von Scherer in the late 19th century. It was discovered in bacteria but later also found in eukaryotes, and was found to be a signaling molecule.

<span class="mw-page-title-main">Phosphatidylinositol (3,4,5)-trisphosphate</span> Chemical compound

Phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3), abbreviated PIP3, is the product of the class I phosphoinositide 3-kinases' (PI 3-kinases) phosphorylation of phosphatidylinositol (4,5)-bisphosphate (PIP2). It is a phospholipid that resides on the plasma membrane.

<span class="mw-page-title-main">Phosphoinositide 3-kinase</span> Class of enzymes

Phosphoinositide 3-kinases (PI3Ks), also called phosphatidylinositol 3-kinases, are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which in turn are involved in cancer.

<span class="mw-page-title-main">Phosphatidylinositol 4,5-bisphosphate</span> Chemical compound

Phosphatidylinositol 4,5-bisphosphate or PtdIns(4,5)P2, also known simply as PIP2 or PI(4,5)P2, is a minor phospholipid component of cell membranes. PtdIns(4,5)P2 is enriched at the plasma membrane where it is a substrate for a number of important signaling proteins. PIP2 also forms lipid clusters that sort proteins.

<span class="mw-page-title-main">Phosphatidylinositol 3-phosphate</span> Chemical compound

Phosphatidylinositol 3-phosphate (PtdIns3P) is a phospholipid found in cell membranes that helps to recruit a range of proteins, many of which are involved in protein trafficking, to the membranes. It is the product of both the class II and III phosphoinositide 3-kinases activity on phosphatidylinositol.

<span class="mw-page-title-main">Phosphatidylinositol 3,4-bisphosphate</span>

Phosphatidylinositol (3,4)-bisphosphate is a minor phospholipid component of cell membranes, yet an important second messenger. The generation of PtdIns(3,4)P2 at the plasma membrane activates a number of important cell signaling pathways.

<span class="mw-page-title-main">Phosphatidylinositol 3,5-bisphosphate</span> Chemical compound

Phosphatidylinositol 3,5-bisphosphate is one of the seven phosphoinositides found in eukaryotic cell membranes. In quiescent cells, the PtdIns(3,5)P2 levels, typically quantified by HPLC, are the lowest amongst the constitutively present phosphoinositides. They are approximately 3 to 5-fold lower as compared to PtdIns3P and PtdIns5P levels, and more than 100-fold lower than the abundant PtdIns4P and PtdIns(4,5)P2. PtdIns(3,5)P2 was first reported to occur in mouse fibroblasts and budding yeast S. cerevisiae in 1997. In S. cerevisiae PtdIns(3,5)P2 levels increase dramatically during hyperosmotic shock. The response to hyperosmotic challenge is not conserved in most tested mammalian cells except for differentiated 3T3L1 adipocytes.

Phosphatidylinositol phosphate kinases (PIPK) are kinases that phosphorylate the phosphoinositides PtdInsP and PtdInsP2 that are derivatives of phosphatidylinositol (PtdIns). It has been found that PtdIns is only phosphorylated on three (3,4,5) of its five hydroxyl groups, possibly because D-2 and D-6 hydroxyl groups cannot be phosphorylated because of steric hindrance. All 7 combinations of phosphorylated PtdIns have been found in animals, all except PtdIns(3,4,5)P3 have been found in plants.

<span class="mw-page-title-main">PX domain</span>

The PX domain is a phosphoinositide-binding structural domain involved in targeting of proteins to cell membranes.

<span class="mw-page-title-main">Yunis–Varon syndrome</span> Medical condition

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The enzyme phosphoinositide 5-phosphatase (EC 3.1.3.36) catalyzes the reaction

<span class="mw-page-title-main">PIKFYVE</span> Protein-coding gene in the species Homo sapiens

PIKfyve, a FYVE finger-containing phosphoinositide kinase, is an enzyme that in humans is encoded by the PIKFYVE gene.

<span class="mw-page-title-main">PIP4K2A</span> Kinase enzyme

Phosphatidylinositol-5-phosphate 4-kinase type-2 alpha is an enzyme that in humans is encoded by the PIP4K2A gene.

<span class="mw-page-title-main">PIP4K2B</span> Protein-coding gene in the species Homo sapiens

Phosphatidylinositol-5-phosphate 4-kinase type-2 beta is an enzyme that in humans is encoded by the PIP4K2B gene.

Bisphosphate may refer to:

<span class="mw-page-title-main">Fig4</span> Protein-coding gene in the species Homo sapiens

Polyphosphoinositide phosphatase also known as phosphatidylinositol 3,5-bisphosphate 5-phosphatase or SAC domain-containing protein 3 (Sac3) is an enzyme that in humans is encoded by the FIG4 gene. Fig4 is an abbreviation for Factor-Induced Gene.

<span class="mw-page-title-main">VAC14</span> Protein-coding gene in the species Homo sapiens

Protein VAC14 homolog, also known as ArPIKfyve, is a protein that in humans is encoded by the VAC14 gene.

Phosphatidylinositol-4,5-bisphosphate 4-phosphatase (EC 3.1.3.78, phosphatidylinositol-4,5-bisphosphate 4-phosphatase I, phosphatidylinositol-4,5-bisphosphate 4-phosphatase II, type I PtdIns-4,5-P2 4-Ptase, type II PtdIns-4,5-P2 4-Ptase, IpgD, PtdIns-4,5-P2 4-phosphatase type I, PtdIns-4,5-P2 4-phosphatase type II, type I phosphatidylinositol-4,5-bisphosphate 4-phosphatase, type 1 4-phosphatase) is an enzyme with systematic name 1-phosphatidyl-1D-myo-inositol-4,5-bisphosphate 4-phosphohydrolase. This enzyme catalyses the following chemical reaction

Phosphatidylinositol-4-phosphate 5-kinases are a class of enzymes that phosphorylate phosphatidylinositol 4-phosphate. They perform this reaction on the fifth hydroxyl of the myo-inositol ring to form phosphatidylinositol 4,5-bisphosphate.

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References

  1. ↑ Di Paolo, Gilbert; De Camilli, Pietro (2006-10-12). "Phosphoinositides in cell regulation and membrane dynamics". Nature. 443 (7112): 651–657. Bibcode:2006Natur.443..651D. doi:10.1038/nature05185. ISSN   1476-4687. PMID   17035995. S2CID   10479545.
  2. ↑ Shisheva, Assia (2003-09-01). "Regulating Glut4 vesicle dynamics by phosphoinositide kinases and phosphoinositide phosphatases". Frontiers in Bioscience: A Journal and Virtual Library. 8 (6): s945–946. doi:10.2741/1101. ISSN   1093-9946. PMID   12957825.
  3. 1 2 Ikonomov, Ognian C.; Sbrissa, Diego; Delvecchio, Khortnal; et al. (2011-04-15). "The phosphoinositide kinase PIKfyve is vital in early embryonic development: preimplantation lethality of PIKfyve-/- embryos but normality of PIKfyve+/- mice". The Journal of Biological Chemistry. 286 (15): 13404–13413. doi: 10.1074/jbc.M111.222364 . ISSN   1083-351X. PMC   3075686 . PMID   21349843.
  4. 1 2 Zhang, Yanling; Zolov, Sergey N.; Chow, Clement Y.; et al. (2007-10-30). "Loss of Vac14, a regulator of the signaling lipid phosphatidylinositol 3,5-bisphosphate, results in neurodegeneration in mice". Proceedings of the National Academy of Sciences of the United States of America. 104 (44): 17518–17523. Bibcode:2007PNAS..10417518Z. doi: 10.1073/pnas.0702275104 . ISSN   0027-8424. PMC   2077288 . PMID   17956977.
  5. ↑ Rameh, L. E.; Tolias, K. F.; Duckworth, B. C.; Cantley, L. C. (1997-11-13). "A new pathway for synthesis of phosphatidylinositol-4,5-bisphosphate". Nature. 390 (6656): 192–196. Bibcode:1997Natur.390..192R. doi:10.1038/36621. ISSN   0028-0836. PMID   9367159. S2CID   4403301.
  6. 1 2 3 4 Sbrissa, Diego; Ikonomov, Ognian C.; Deeb, Robert; Shisheva, Assia (2002-12-06). "Phosphatidylinositol 5-phosphate biosynthesis is linked to PIKfyve and is involved in osmotic response pathway in mammalian cells". The Journal of Biological Chemistry. 277 (49): 47276–47284. doi: 10.1074/jbc.M207576200 . ISSN   0021-9258. PMID   12270933.
  7. 1 2 Morris, J. B.; Hinchliffe, K. A.; Ciruela, A.; et al. (2000-06-09). "Thrombin stimulation of platelets causes an increase in phosphatidylinositol 5-phosphate revealed by mass assay". FEBS Letters. 475 (1): 57–60. doi:10.1016/s0014-5793(00)01625-2. ISSN   0014-5793. PMID   10854858. S2CID   41475679.
  8. 1 2 Sarkes, Deborah; Rameh, Lucia E. (2010-05-27). "A novel HPLC-based approach makes possible the spatial characterization of cellular PtdIns5P and other phosphoinositides". The Biochemical Journal. 428 (3): 375–384. doi:10.1042/BJ20100129. ISSN   1470-8728. PMC   2944655 . PMID   20370717.
  9. 1 2 Zou, Jun; Marjanovic, Jasna; Kisseleva, Marina V.; et al. (2007-10-23). "Type I phosphatidylinositol-4,5-bisphosphate 4-phosphatase regulates stress-induced apoptosis". Proceedings of the National Academy of Sciences of the United States of America. 104 (43): 16834–16839. Bibcode:2007PNAS..10416834Z. doi: 10.1073/pnas.0708189104 . ISSN   0027-8424. PMC   2040409 . PMID   17940011.
  10. 1 2 Grainger, Deborah L.; Tavelis, Christodoulos; Ryan, Alexander J.; Hinchliffe, Katherine A. (2012). "The emerging role of PtdIns5P: another signalling phosphoinositide takes its place". Biochemical Society Transactions. 40 (1): 257–261. doi:10.1042/BST20110617. ISSN   1470-8752. PMID   22260701.
  11. ↑ Sbrissa, D.; Ikonomov, O. C.; Shisheva, A. (1999-07-30). "PIKfyve, a mammalian ortholog of yeast Fab1p lipid kinase, synthesizes 5-phosphoinositides. Effect of insulin". The Journal of Biological Chemistry. 274 (31): 21589–21597. doi: 10.1074/jbc.274.31.21589 . ISSN   0021-9258. PMID   10419465.
  12. ↑ Shisheva, A. (2001). "PIKfyve: the road to PtdIns 5-P and PtdIns 3,5-P(2)". Cell Biology International. 25 (12): 1201–1206. doi:10.1006/cbir.2001.0803. ISSN   1065-6995. PMID   11748912. S2CID   29411107.
  13. ↑ Tolias, K. F.; Rameh, L. E.; Ishihara, H.; et al. (1998-07-17). "Type I phosphatidylinositol-4-phosphate 5-kinases synthesize the novel lipids phosphatidylinositol 3,5-bisphosphate and phosphatidylinositol 5-phosphate". The Journal of Biological Chemistry. 273 (29): 18040–18046. doi: 10.1074/jbc.273.29.18040 . ISSN   0021-9258. PMID   9660759.
  14. ↑ Shisheva, Assia (2008). "PIKfyve: Partners, significance, debates and paradoxes". Cell Biology International. 32 (6): 591–604. doi:10.1016/j.cellbi.2008.01.006. ISSN   1065-6995. PMC   2491398 . PMID   18304842.
  15. 1 2 Coronas, S.; Lagarrigue, F.; Ramel, D.; et al. (2008-07-25). "Elevated levels of PtdIns5P in NPM-ALK transformed cells: implication of PIKfyve". Biochemical and Biophysical Research Communications. 372 (2): 351–355. doi:10.1016/j.bbrc.2008.05.062. ISSN   1090-2104. PMID   18501703.
  16. ↑ Sbrissa, Diego; Ikonomov, Ognian C.; Strakova, Jana; et al. (2004). "A mammalian ortholog of Saccharomyces cerevisiae Vac14 that associates with and up-regulates PIKfyve phosphoinositide 5-kinase activity". Molecular and Cellular Biology. 24 (23): 10437–10447. doi:10.1128/MCB.24.23.10437-10447.2004. ISSN   0270-7306. PMC   529046 . PMID   15542851.
  17. ↑ Tronchère, Hélène; Laporte, Jocelyn; Pendaries, Caroline; et al. (2004-02-20). "Production of phosphatidylinositol 5-phosphate by the phosphoinositide 3-phosphatase myotubularin in mammalian cells". The Journal of Biological Chemistry. 279 (8): 7304–7312. doi: 10.1074/jbc.M311071200 . ISSN   0021-9258. PMID   14660569.
  18. ↑ Vaccari, Ilaria; Dina, Giorgia; Tronchère, Hélène; et al. (2011). "Genetic interaction between MTMR2 and FIG4 phospholipid phosphatases involved in Charcot-Marie-Tooth neuropathies". PLOS Genetics. 7 (10): e1002319. doi: 10.1371/journal.pgen.1002319 . ISSN   1553-7404. PMC   3197679 . PMID   22028665.
  19. ↑ Sbrissa, Diego; Ikonomov, Ognian C.; Fu, Zhiyao; et al. (2007-08-17). "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". The Journal of Biological Chemistry. 282 (33): 23878–23891. doi: 10.1074/jbc.M611678200 . ISSN   0021-9258. PMID   17556371.
  20. ↑ Ikonomov, Ognian C.; Sbrissa, Diego; Fenner, Homer; Shisheva, Assia (2009-12-18). "PIKfyve-ArPIKfyve-Sac3 core complex: contact sites and their consequence for Sac3 phosphatase activity and endocytic membrane homeostasis". The Journal of Biological Chemistry. 284 (51): 35794–35806. doi: 10.1074/jbc.M109.037515 . ISSN   1083-351X. PMC   2791009 . PMID   19840946.
  21. ↑ Niebuhr, Kirsten; Giuriato, Sylvie; Pedron, Thierry; et al. (2002-10-01). "Conversion of PtdIns(4,5)P(2) into PtdIns(5)P by the S.flexneri effector IpgD reorganizes host cell morphology". The EMBO Journal. 21 (19): 5069–5078. doi:10.1093/emboj/cdf522. ISSN   0261-4189. PMC   129044 . PMID   12356723.
  22. ↑ Ungewickell, Alexander; Hugge, Christopher; Kisseleva, Marina; et al. (2005-12-27). "The identification and characterization of two phosphatidylinositol-4,5-bisphosphate 4-phosphatases". Proceedings of the National Academy of Sciences of the United States of America. 102 (52): 18854–18859. Bibcode:2005PNAS..10218854U. doi: 10.1073/pnas.0509740102 . ISSN   0027-8424. PMC   1323219 . PMID   16365287.
  23. ↑ Sbrissa, Diego; Ikonomov, Ognian C.; Strakova, Jana; Shisheva, Assia (2004). "Role for a novel signaling intermediate, phosphatidylinositol 5-phosphate, in insulin-regulated F-actin stress fiber breakdown and GLUT4 translocation". Endocrinology. 145 (11): 4853–4865. doi:10.1210/en.2004-0489. ISSN   0013-7227. PMID   15284192.
  24. 1 2 Guittard, Geoffrey; Gérard, Audrey; Dupuis-Coronas, Sophie; et al. (2009-04-01). "Cutting edge: Dok-1 and Dok-2 adaptor molecules are regulated by phosphatidylinositol 5-phosphate production in T cells". Journal of Immunology. 182 (7): 3974–3978. doi:10.4049/jimmunol.0804172. ISSN   1550-6606. PMID   19299694.
  25. ↑ Roberts, Hilary F.; Clarke, Jonathan H.; Letcher, Andrew J.; et al. (2005-05-23). "Effects of lipid kinase expression and cellular stimuli on phosphatidylinositol 5-phosphate levels in mammalian cell lines". FEBS Letters. 579 (13): 2868–2872. doi:10.1016/j.febslet.2005.04.027. ISSN   0014-5793. PMID   15876433.
  26. ↑ Barlow, Christy A.; Laishram, Rakesh S.; Anderson, Richard A. (2010). "Nuclear phosphoinositides: a signaling enigma wrapped in a compartmental conundrum". Trends in Cell Biology. 20 (1): 25–35. doi:10.1016/j.tcb.2009.09.009. ISSN   1879-3088. PMC   2818233 . PMID   19846310.
  27. ↑ Clarke, J. H.; Letcher, A. J.; D'santos, C. S.; et al. (2001-08-01). "Inositol lipids are regulated during cell cycle progression in the nuclei of murine erythroleukaemia cells". The Biochemical Journal. 357 (Pt 3): 905–910. doi:10.1042/0264-6021:3570905. ISSN   0264-6021. PMC   1222024 . PMID   11463365.
  28. ↑ Jones, David R.; Bultsma, Yvette; Keune, Willem-Jan; et al. (2006-09-01). "Nuclear PtdIns5P as a transducer of stress signaling: an in vivo role for PIP4Kbeta". Molecular Cell. 23 (5): 685–695. doi: 10.1016/j.molcel.2006.07.014 . ISSN   1097-2765. PMID   16949365.
  29. ↑ Gozani, Or; Karuman, Philip; Jones, David R.; et al. (2003-07-11). "The PHD finger of the chromatin-associated protein ING2 functions as a nuclear phosphoinositide receptor". Cell. 114 (1): 99–111. doi: 10.1016/s0092-8674(03)00480-x . ISSN   0092-8674. PMID   12859901.
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