Regulates Rhodopsin-1 Metabolism and Is Required for Photoreceptor Neuron Survival
Tight regulation of the visual response is essential for photoreceptor function and survival. Visual response dysregulation often leads to photoreceptor cell degeneration, but the causes of such cell death are not well understood. In this study, we investigated a fatty acid transport protein (fatp) null mutation that caused adult-onset and progressive photoreceptor cell death. Consistent with fatp having a role in the retina, we showed that fatp is expressed in adult photoreceptors and accessory cells and that its re-expression in photoreceptors rescued photoreceptor viability in fatp mutants. The visual response in young fatp-mutant flies was abnormal with elevated electroretinogram amplitudes associated with high levels of Rhodopsin-1 (Rh1). Reducing Rh1 levels in rh1 mutants or depriving flies of vitamin A rescued photoreceptor cell death in fatp mutant flies. Our results indicate that fatp promotes photoreceptor survival by regulating Rh1 abundance.
Vyšlo v časopise:
Regulates Rhodopsin-1 Metabolism and Is Required for Photoreceptor Neuron Survival. PLoS Genet 8(7): e32767. doi:10.1371/journal.pgen.1002833
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1002833
Souhrn
Tight regulation of the visual response is essential for photoreceptor function and survival. Visual response dysregulation often leads to photoreceptor cell degeneration, but the causes of such cell death are not well understood. In this study, we investigated a fatty acid transport protein (fatp) null mutation that caused adult-onset and progressive photoreceptor cell death. Consistent with fatp having a role in the retina, we showed that fatp is expressed in adult photoreceptors and accessory cells and that its re-expression in photoreceptors rescued photoreceptor viability in fatp mutants. The visual response in young fatp-mutant flies was abnormal with elevated electroretinogram amplitudes associated with high levels of Rhodopsin-1 (Rh1). Reducing Rh1 levels in rh1 mutants or depriving flies of vitamin A rescued photoreceptor cell death in fatp mutant flies. Our results indicate that fatp promotes photoreceptor survival by regulating Rh1 abundance.
Zdroje
1. SohockiMMDaigerSPBowneSJRodriquezJANorthrupH 2001 Prevalence of mutations causing retinitis pigmentosa and other inherited retinopathies. Hum Mutat 17 42 51
2. LeeESFlanneryJG 2007 Transport of truncated rhodopsin and its effects on rod function and degeneration. Invest Ophthalmol Vis Sci 48 2868 2876
3. MollereauBDomingosPM 2005 Photoreceptor differentiation in Drosophila: from immature neurons to functional photoreceptors. Dev Dyn 232 585 592
4. WangTMontellC 2007 Phototransduction and retinal degeneration in Drosophila. Pflugers Arch 454 821 847
5. ShiehBH 2011 Molecular genetics of retinal degeneration: A Drosophila perspective. Fly (Austin) 5
6. GalyARouxMJSahelJALeveillardTGiangrandeA 2005 Rhodopsin maturation defects induce photoreceptor death by apoptosis: a fly model for RhodopsinPro23His human retinitis pigmentosa. Hum Mol Genet 14 2547 2557
7. GambisADourlenPStellerHMollereauB 2011 Two-color in vivo imaging of photoreceptor apoptosis and development in Drosophila. Dev Biol 351 128 134
8. WatkinsPAMaiguelDJiaZPevsnerJ 2007 Evidence for 26 distinct acyl-coenzyme A synthetase genes in the human genome. J Lipid Res 48 2736 2750
9. WatkinsPA 2008 Very-long-chain acyl-CoA synthetases. J Biol Chem 283 1773 1777
10. GimenoRE 2007 Fatty acid transport proteins. Curr Opin Lipidol 18 271 276
11. SchafferJELodishHF 1994 Expression cloning and characterization of a novel adipocyte long chain fatty acid transport protein. Cell 79 427 436
12. GuignardTJJinMPequignotMOLiSChassigneuxY 2010 FATP1 inhibits 11-cis retinol formation via interaction with the visual cycle retinoid isomerase RPE65 and lecithin:retinol acyltransferase. J Biol Chem 285 18759 18768
13. HerrmannTBuchkremerFGoschIHallAMBernlohrDA 2001 Mouse fatty acid transport protein 4 (FATP4): characterization of the gene and functional assessment as a very long chain acyl-CoA synthetase. Gene 270 31 40
14. StahlA 2004 A current review of fatty acid transport proteins (SLC27). Pflugers Arch 447 722 727
15. HerrmannTvan der HoevenFGroneHJStewartAFLangbeinL 2003 Mice with targeted disruption of the fatty acid transport protein 4 (Fatp 4, Slc27a4) gene show features of lethal restrictive dermopathy. J Cell Biol 161 1105 1115
16. MoulsonCLMartinDRLugusJJSchafferJELindAC 2003 Cloning of wrinkle-free, a previously uncharacterized mouse mutation, reveals crucial roles for fatty acid transport protein 4 in skin and hair development. Proc Natl Acad Sci U S A 100 5274 5279
17. KlarJSchweigerMZimmermanRZechnerRLiH 2009 Mutations in the fatty acid transport protein 4 gene cause the ichthyosis prematurity syndrome. Am J Hum Genet 85 248 253
18. GolicKG 1991 Site-specific recombination between homologous chromosomes in Drosophila. Science 252 958 961
19. MollereauBWernetMFBeaufilsPKillianDPichaudF 2000 A green fluorescent protein enhancer trap screen in Drosophila photoreceptor cells. Mech Dev 93 151 160
20. PichaudFDesplanC 2001 A new visualization approach for identifying mutations that affect differentiation and organization of the Drosophila ommatidia. Development 128 815 826
21. BrandAHPerrimonN 1993 Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 118 401 415
22. StowersRSSchwarzTL 1999 A genetic method for generating Drosophila eyes composed exclusively of mitotic clones of a single genotype. Genetics 152 1631 1639
23. KuradaPO'TousaJE 1995 Retinal degeneration caused by dominant rhodopsin mutations in Drosophila. Neuron 14 571 579
24. ColleyNJCassillJABakerEKZukerCS 1995 Defective intracellular transport is the molecular basis of rhodopsin-dependent dominant retinal degeneration. Proc Natl Acad Sci U S A 92 3070 3074
25. HarrisWAStarkWS 1977 Hereditary retinal degeneration in Drosophila melanogaster. A mutant defect associated with the phototransduction process. J Gen Physiol 69 261 291
26. AllowayPGHowardLDolphPJ 2000 The formation of stable rhodopsin-arrestin complexes induces apoptosis and photoreceptor cell degeneration. Neuron 28 129 138
27. JohnsonKGraweFGrzeschikNKnustE 2002 Drosophila crumbs is required to inhibit light-induced photoreceptor degeneration. Curr Biol 12 1675 1680
28. ChinchoreYMitraADolphPJ 2009 Accumulation of rhodopsin in late endosomes triggers photoreceptor cell degeneration. PLoS Genet 5 e1000377 doi:10.1371/journal.pgen.1000377
29. SatohAKReadyDF 2005 Arrestin1 mediates light-dependent rhodopsin endocytosis and cell survival. Curr Biol 15 1722 1733
30. KiselevASocolichMVinosJHardyRWZukerCS 2000 A molecular pathway for light-dependent photoreceptor apoptosis in Drosophila. Neuron 28 139 152
31. XuHLeeSJSuzukiEDuganKDStoddardA 2004 A lysosomal tetraspanin associated with retinal degeneration identified via a genome-wide screen. Embo J 23 811 822
32. AcharyaUPatelSKoundakjianENagashimaKHanX 2003 Modulating sphingolipid biosynthetic pathway rescues photoreceptor degeneration. Science 299 1740 1743
33. YonamineIBambaTNiralaNKJesminNKosakowska-CholodyT 2011 Sphingosine kinases and their metabolites modulate endolysosomal trafficking in photoreceptors. J Cell Biol 192 557 567
34. AcharyaUMowenMBNagashimaKAcharyaJK 2004 Ceramidase expression facilitates membrane turnover and endocytosis of rhodopsin in photoreceptors. Proc Natl Acad Sci U S A 101 1922 1926
35. WangXWangTJiaoYvon LintigJMontellC 2010 Requirement for an enzymatic visual cycle in Drosophila. Curr Biol 20 93 102
36. WangXWangTNiJDvon LintigJMontellC 2012 The Drosophila visual cycle and de novo chromophore synthesis depends on rdhB. J Neurosci 32 3485 3491
37. MontellC 2012 Drosophila visual transduction. Trends Neurosci
38. LeeSJXuHMontellC 2004 Rhodopsin kinase activity modulates the amplitude of the visual response in Drosophila. Proc Natl Acad Sci U S A 101 11874 11879
39. HardieRCMartinFChybSRaghuP 2003 Rescue of light responses in the Drosophila “null” phospholipase C mutant, norpAP24, by the diacylglycerol kinase mutant, rdgA, and by metabolic inhibition. J Biol Chem 278 18851 18858
40. ChybSRaghuPHardieRC 1999 Polyunsaturated fatty acids activate the Drosophila light-sensitive channels TRP and TRPL. Nature 397 255 259
41. LeungHTTseng-CrankJKimEMahapatraCShinoS 2008 DAG lipase activity is necessary for TRP channel regulation in Drosophila photoreceptors. Neuron 58 884 896
42. MendesCSLevetCChatelainGDourlenPFouilletA 2009 ER stress protects from retinal degeneration. EMBO J 28 1296 1307
43. LeeYSCarthewRW 2003 Making a better RNAi vector for Drosophila: use of intron spacers. Methods 30 322 329
44. FishMPGrothACCalosMPNusseR 2007 Creating transgenic Drosophila by microinjecting the site-specific phiC31 integrase mRNA and a transgene-containing donor plasmid. Nat Protoc 2 2325 2331
45. DomingosPMMlodzikMMendesCSBrownSStellerH 2004 Spalt transcription factors are required for R3/R4 specification and establishment of planar cell polarity in the Drosophila eye. Development 131 5695 5702
46. DomingosPMBrownSBarrioRRatnakumarKFrankfortBJ 2004 Regulation of R7 and R8 differentiation by the spalt genes. Dev Biol 273 121 133
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
2012 Číslo 7
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