#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

A Dependent Pool of Phosphatidylinositol 4,5 Bisphosphate (PIP) Is Required for G-Protein Coupled Signal Transduction in Photoreceptors


PIP2 has been implicated in multiple functions at the plasma membrane. Some of these require its hydrolysis by receptor-activated phospholipase C, whereas others, such as membrane transport and cytoskeletal function, involve the interaction of the intact lipid with cellular proteins. The mechanistic basis underlying the segregation of these two classes of PIP2 dependent functions is unknown; it has been postulated that this might involve unique pools of PIP2 generated by distinct phosphoinsoitide kinases. We have studied this question in Drosophila photoreceptors, a model system where sensory transduction requires robust phospholipase C mediated PIP2 hydrolysis. We find that the activity of phosphatidylinositol-4-phosphate 5 kinase encoded by dPIP5K is required to support normal sensory transduction and PIP2 dynamics in photoreceptors. Remarkably, non-PLC dependent functions of PIP2, such as vesicular transport and the actin cytoskeleton, were unaffected in dPIP5K mutants. Thus, dPIP5K supports a pool of PIP2 that is readily available to PLC, but has no role in sustaining other non-PLC mediated PIP2 dependent processes. These findings support the existence of at least two non-overlapping pools of PIP2 at the plasma membrane, and provide a platform for future studies of PIP2 regulation at the plasma membrane.


Vyšlo v časopise: A Dependent Pool of Phosphatidylinositol 4,5 Bisphosphate (PIP) Is Required for G-Protein Coupled Signal Transduction in Photoreceptors. PLoS Genet 11(1): e32767. doi:10.1371/journal.pgen.1004948
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004948

Souhrn

PIP2 has been implicated in multiple functions at the plasma membrane. Some of these require its hydrolysis by receptor-activated phospholipase C, whereas others, such as membrane transport and cytoskeletal function, involve the interaction of the intact lipid with cellular proteins. The mechanistic basis underlying the segregation of these two classes of PIP2 dependent functions is unknown; it has been postulated that this might involve unique pools of PIP2 generated by distinct phosphoinsoitide kinases. We have studied this question in Drosophila photoreceptors, a model system where sensory transduction requires robust phospholipase C mediated PIP2 hydrolysis. We find that the activity of phosphatidylinositol-4-phosphate 5 kinase encoded by dPIP5K is required to support normal sensory transduction and PIP2 dynamics in photoreceptors. Remarkably, non-PLC dependent functions of PIP2, such as vesicular transport and the actin cytoskeleton, were unaffected in dPIP5K mutants. Thus, dPIP5K supports a pool of PIP2 that is readily available to PLC, but has no role in sustaining other non-PLC mediated PIP2 dependent processes. These findings support the existence of at least two non-overlapping pools of PIP2 at the plasma membrane, and provide a platform for future studies of PIP2 regulation at the plasma membrane.


Zdroje

1. Klopfenstein DR, Tomishige M, Stuurman N, Vale RD (2002) Role of phosphatidylinositol(4,5)bisphosphate organization in membrane transport by the Unc104 kinesin motor. Cell 109: 347–358. 12015984

2. Moss SE (2012) How actin gets the PIP. Sci Signal 5: pe7. doi: 10.1126/scisignal.2002839 22375053

3. Hilgemann DW, Feng S, Nasuhoglu C (2001) The Complex and Intriguing Lives of PIP2 with Ion Channels and Transporters. Sci STKE 2001: RE19. 11734659

4. Mccrea HJ, De Camilli P (2009) Mutations in Phosphoinositide Metabolizing Enzymes and Human Disease Mutations in Phosphoinositide Metabolizing Enzymes and Human Disease. Physiol 24: 8–16.

5. Ackermann KE, Gish BG, Honchar MP, Sherman WR (1987) Evidence that inositol 1-phosphate in brain of lithium-treated rats results mainly from phosphatidylinositol metabolism. Biochem J 242: 517–524. 3036092

6. Hinchliffe KA, Ciruela A, Irvine RF (1998) PIPkins1, their substrates and their products: new functions for old enzymes. Biochim Biophys Acta 1436: 87–104. 9838059

7. Kunz J, Wilson MP, Kisseleva M, Hurley JH, Majerus PW, et al. (2000) The activation loop of phosphatidylinositol phosphate kinases determines signaling specificity. Mol Cell 5: 1–11. 10678164

8. Kunz J, Fuelling A, Kolbe L, Anderson RA (2002) Stereo-specific substrate recognition by phosphatidylinositol phosphate kinases is swapped by changing a single amino acid residue. J Biol Chem 277: 5611–9. 11733501

9. Hardie RC, Raghu P (2001) Visual transduction in Drosophila. Nature 413: 186–93.

10. Raghu P, Hardie RC (2009) Regulation of Drosophila TRPC channels by lipid messengers. Cell Calcium 45: 566–573. 19362736

11. Raghu P, Yadav S, Mallampati NBN (2012) Lipid signaling in Drosophila photoreceptors. Biochim Biophys Acta 1821: 1154–1165. 22487656

12. Cooke FT, Dove SK, McEwen RK, Painter G, Holmes AB, et al. (1998) The stress-activated phosphatidylinositol 3-phosphate 5-kinase Fab1p is essential for vacuole function in S. cerevisiae. Curr Biol 8: 1219–1222. 9811604

13. Rusten TE, Rodahl LM, Pattni K, Englund C, Samakovlis C, et al. (2006) Fab1 phosphatidylinositol 3-phosphate 5-kinase controls trafficking but not silencing of endocytosed receptors. Mol Biol Cell 17: 3989–4001. 16837550

14. Gupta A, Toscano S, Trivedi D, Jones DR, Mathre S, et al. (2013) Phosphatidylinositol 5-phosphate 4-kinase (PIP4K) regulates TOR signaling and cell growth during Drosophila development. Proc Natl Acad Sci U S A 110: 5963–5968. doi: 10.1073/pnas.1219333110 23530222

15. Hassan BA, Prokopenko SN, Breuer S, Zhang B, Paululat A, et al. (1998) skittles, a Drosophila phosphatidylinositol 4-phosphate 5-kinase, is required for cell viability, germline development and bristle morphology, but not for neurotransmitter release. Genetics 150: 1527–1537. 9832529

16. Gervais L, Claret S, Januschke J, Roth S, Guichet A (2008) PIP5K-dependent production of PIP2 sustains microtubule organization to establish polarized transport in the Drosophila oocyte. Development 135: 3829–3838. doi: 10.1242/dev.029009 18948416

17. Loijens JC, Anderson RA (1996) Type I phosphatidylinositol-4-phosphate 5-kinases are distinct members of this novel lipid kinase family. 271: 32937–32943. 8955136

18. Wenk MR, Pellegrini L, Klenchin VA, Di Paolo G, Chang S, et al. (2001) PIP kinase Igamma is the major PI(4,5)P(2) synthesizing enzyme at the synapse. Neuron 32: 79–88. 11604140

19. Giudici M-L, Emson PC, Irvine RF (2004) A novel neuronal-specific splice variant of Type I phosphatidylinositol 4-phosphate 5-kinase isoform gamma. Biochem J 379: 489–496. 14741049

20. Gong WJ, Golic KG (2003) Ends-out, or replacement, gene targeting in Drosophila. Proc Natl Acad Sci U S A 100: 2556–2561. 12589026

21. Xu T, Rubin GM (1993) Analysis Of Genetic Mosaics In Developing and Adult Drosophila Tissues. Development 117: 1223–1237. 8404527

22. Stowers RS, Schwarz TL (1999) A genetic method for generating Drosophila eyes composed exclusively of mitotic clones of a single genotype. Genetics 152: 1631–1639. 10430588

23. Harris WA, Stark WS (1977) Hereditary retinal degeneration in Drosophila melanogaster. A mutant defect associated with the phototransduction process. JGenPhysiol 69: 261–91. 139462

24. Scott K, Becker A, Sun Y, Hardy R, Zuker C (1995) Gq alpha protein function in vivo: genetic dissection of its role in photoreceptor cell physiology. Neuron 15: 919–927. 7576640

25. Coppolino MG, Dierckman R, Loijens J, Collins RF, Pouladi M, et al. (2002) Inhibition of phosphatidylinositol-4-phosphate 5-kinase Ialpha impairs localized actin remodeling and suppresses phagocytosis. J Biol Chem 277: 43849–43857. 12223494

26. Bretscher A (1999) Regulation of cortical structure by the ezrin-radixin-moesin protein family. Curr Opin Cell Biol 11: 109–116. 10047517

27. Fiévet B, Louvard D, Arpin M (2007) ERM proteins in epithelial cell organization and functions. Biochim Biophys Acta 1773: 653–660.

28. Yonemura S, Matsui T, Tsukita S, Tsukita S (2002) Rho-dependent and -independent activation mechanisms of ezrin / radixin / moesin proteins: an essential role for polyphosphoinositides in vivo. J Cell Sci 115: 2569–2580. 12045227

29. Karagiosis SA, Ready DF (2004) Moesin contributes an essential structural role in Drosophila photoreceptor morphogenesis. Development 131: 725–732. 14724125

30. Satoh AK, O’Tousa JE, Ozaki K, Ready DF (2005) Rab11 mediates post-Golgi trafficking of rhodopsin to the photosensitive apical membrane of Drosophila photoreceptors. JCellSci 132: 1487–1497. 15728675

31. Zoncu R, Perera RM, Sebastian R, Nakatsu F, Chen H, et al. (2007) Loss of endocytic clathrin-coated pits upon acute depletion of phosphatidylinositol 4,5-bisphosphate. Proc Natl Acad Sci U S A 104: 3793–3798. 17360432

32. Alloway PG, Howard L, Dolph PJ (2000) The formation of stable rhodopsin-arrestin complexes induces apoptosis and photoreceptor cell degeneration. Neuron 28: 129–38. 11086989

33. Kiselev A, Socolich M, Vinos J, Hardy RW, Zuker CS, et al. (2000) A molecular pathway for light-dependent photorecptor apoptosis in Drosophila. Neuron 28: 139–152. 11086990

34. Toba G, Ohsako T, Miyata N, Ohtsuka T, Seong K-H, et al. (1999) The Gene Search System: A Method for Efficient Detection and Rapid Molecular Identification of Genes in Drosophila melanogaster. Genet 151: 725–737. 9927464

35. Trivedi D, Padinjat R (2007) RdgB proteins: Functions in lipid homeostasis and signal transduction. Biochim Biophys Acta 1771: 692–699. 17543578

36. Hardie RC, Raghu P, Moore S, Juusola M, Baines RA, et al. (2001) Calcium influx via TRP channels is required to maintain PIP2 levels in Drosophila photoreceptors. Neuron 30: 149–59. 11343651

37. King CE, Stephens LR, Hawkins PT, Guy GR, Michell RH (1987) Multiple metabolic pools of phosphoinositides and phosphatidate in human erythrocytes incubated in a medium that permits rapid transmembrane exchange of phosphate. Biochem J 244: 209–217. 2821998

38. Rameh LE, Tolias KF, Duckworth BC, Cantley LC (1997) A new pathway for synthesis of phosphatidylinositol-4,5-bisphosphate. Nature 390: 192–196. 9367159

39. Nakatsu F, Baskin JM, Chung J, Tanner LB, Shui G, et al. (2012) PtdIns4P synthesis by PI4KIIIα at the plasma membrane and its impact on plasma membrane identity. J Cell Biol 199: 1003–1016. doi: 10.1083/jcb.201206095 23229899

40. Orem NR, Dolph PJ (2002) Loss of the phospholipase C gene product induces massive endocytosis of rhodopsin and arrestin in Drosophila photoreceptors. Vision Res 42: 497–505. 11853766

41. Chang HY, Ready DF (2000) Rescue of photoreceptor degeneration in rhodopsin-null Drosophila mutants by activated Rac1. Science (80-) 290: 1978–80. 11110667

42. Raghu P, Coessens E, Manifava M, Georgiev P, Pettitt T, et al. (2009) Rhabdomere biogenesis in Drosophila photoreceptors is acutely sensitive to phosphatidic acid levels. J Cell Biol 185: 129–145. doi: 10.1083/jcb.200807027 19349583

43. Fabian L, Wei HC, Rollins J, Noguchi T, Blankenship JT, et al. (2010) Phosphatidylinositol 4,5-bisphosphate directs spermatid cell polarity and exocyst localization in Drosophila. Mol Biol Cell 21: 1546–1555. doi: 10.1091/mbc.E09-07-0582 20237161

44. Gervais L, Claret S, Januschke J, Roth S, Guichet A (2008) PIP5K-dependent production of PIP2 sustains microtubule organization to establish polarized transport in the Drosophila oocyte. Development 135: 3829–3838. doi: 10.1242/dev.029009 18948416

45. Willars GB, Nahorski SR, Challiss RA (1998) Differential regulation of muscarinic acetylcholine receptor-sensitive polyphosphoinositide pools and consequences for signaling in human neuroblastoma cells. J Biol Chem 273: 5037–5046. 9478953

46. Várnai P, Balla T (1998) Visualization of phosphoinositides that bind pleckstrin homology domains: calcium- and agonist-induced dynamic changes and relationship to myo-[3H]inositol-labeled phosphoinositide pools. J Cell Biol 143: 501–510.

47. Balla A, Kim YJ, Varnai P, Szentpetery Z, Knight Z, et al. (2008) Maintenance of hormone-sensitive phosphoinositide pools in the plasma membrane requires phosphatidylinositol 4-kinase IIIalpha. Mol Biol Cell 19: 711–721. 18077555

48. Kennedy ED, Challiss RA, Ragan CI, Nahorski SR (1990) Reduced inositol polyphosphate accumulation and inositol supply induced by lithium in stimulated cerebral cortex slices. 267: 781–786. 2339988

49. Wang Y, Chen X, Lian L, Tang T, Stalker TJ, et al. (2008) Loss of PIP5KIbeta demonstrates that PIP5KI isoform-specific PIP2 synthesis is required for IP3 formation. Proc Natl Acad Sci U S A 105: 14064–14069. doi: 10.1073/pnas.0804139105 18772378

50. Di Paolo G, Pellegrini L, Letinic K, Cestra G, Zoncu R, et al. (2002) Recruitment and regulation of phosphatidylinositol phosphate kinase type 1 gamma by the FERM domain of talin. Nature 420: 85–89. 12422219

51. Ling K, Doughman RL, Firestone AJ, Bunce MW, Anderson RA (2002) Type I gamma phosphatidylinositol phosphate kinase targets and regulates focal adhesions. Nature 420: 89–93. 12422220

52. Sanxaridis PD, Cronin MA, Rawat SS, Waro G, Acharya U, et al. (2007) Light-induced recruitment of INAD-signaling complexes to detergent-resistant lipid rafts in Drosophila photoreceptors. Mol Cell Neurosci 36: 36–46. 17689976

53. Pike LJ, Miller JM (1998) Cholesterol depletion delocalizes phosphatidylinositol bisphosphate and inhibits hormone-stimulated phosphatidylinositol turnover. J Biol Chem 273: 22298–22304. 9712847

54. Morris JB, Huynh H, Vasilevski O, Woodcock EA (2006) Alpha1-adrenergic receptor signaling is localized to caveolae in neonatal rat cardiomyocytes. J Mol Cell Cardiol 41: 17–25. 16730745

55. Rong YS, Titen SW, Xie HB, Golic MM, Bastiani M, et al. (2002) Targeted mutagenesis by homologous recombination in D. melanogaster. Genes Dev 16: 1568–1581. 12080094

56. Venken KJT, He Y, Hoskins RA, Bellen HJ (2006) P[acman]: a BAC transgenic platform for targeted insertion of large DNA fragments in D. melanogaster. Science 314: 1747–1751. 17138868

57. Georgiev P, Garcia-Murillas I, Ulahannan D, Hardie RC, Raghu P (2005) Functional INAD complexes are required to mediate degeneration in photoreceptors of the Drosophila rdgA mutant. J Cell Sci 118: 1373–1384. 15755798

58. Fujita SC, Inoue H, Yoshioka T, Hotta Y (1987) Quantitative tissue isolation from Drosophila freeze-dried in acetone. Biochem J 243: 97–104. 3111462

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2015 Číslo 1
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Aktuální možnosti diagnostiky a léčby litiáz
nový kurz
Autori: MUDr. Tomáš Ürge, PhD.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#