#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Localization of a Guanylyl Cyclase to Chemosensory Cilia Requires the Novel Ciliary MYND Domain Protein DAF-25


In harsh conditions, Caenorhabditis elegans arrests development to enter a non-aging, resistant diapause state called the dauer larva. Olfactory sensation modulates the TGF-β and insulin signaling pathways to control this developmental decision. Four mutant alleles of daf-25 (abnormal DAuer Formation) were isolated from screens for mutants exhibiting constitutive dauer formation and found to be defective in olfaction. The daf-25 dauer phenotype is suppressed by daf-10/IFT122 mutations (which disrupt ciliogenesis), but not by daf-6/PTCHD3 mutations (which prevent environmental exposure of sensory cilia), implying that DAF-25 functions in the cilia themselves. daf-25 encodes the C. elegans ortholog of mammalian Ankmy2, a MYND domain protein of unknown function. Disruption of DAF-25, which localizes to sensory cilia, produces no apparent cilia structure anomalies, as determined by light and electron microscopy. Hinting at its potential function, the dauer phenotype, epistatic order, and expression profile of daf-25 are similar to daf-11, which encodes a cilium-localized guanylyl cyclase. Indeed, we demonstrate that DAF-25 is required for proper DAF-11 ciliary localization. Furthermore, the functional interaction is evolutionarily conserved, as mouse Ankmy2 interacts with guanylyl cyclase GC1 from ciliary photoreceptors. The interaction may be specific because daf-25 mutants have normally-localized OSM-9/TRPV4, TAX-4/CNGA1, CHE-2/IFT80, CHE-11/IFT140, CHE-13/IFT57, BBS-8, OSM-5/IFT88, and XBX-1/D2LIC in the cilia. Intraflagellar transport (IFT) (required to build cilia) is not defective in daf-25 mutants, although the ciliary localization of DAF-25 itself is influenced in che-11 mutants, which are defective in retrograde IFT. In summary, we have discovered a novel ciliary protein that plays an important role in cGMP signaling by localizing a guanylyl cyclase to the sensory organelle.


Vyšlo v časopise: Localization of a Guanylyl Cyclase to Chemosensory Cilia Requires the Novel Ciliary MYND Domain Protein DAF-25. PLoS Genet 6(11): e32767. doi:10.1371/journal.pgen.1001199
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1001199

Souhrn

In harsh conditions, Caenorhabditis elegans arrests development to enter a non-aging, resistant diapause state called the dauer larva. Olfactory sensation modulates the TGF-β and insulin signaling pathways to control this developmental decision. Four mutant alleles of daf-25 (abnormal DAuer Formation) were isolated from screens for mutants exhibiting constitutive dauer formation and found to be defective in olfaction. The daf-25 dauer phenotype is suppressed by daf-10/IFT122 mutations (which disrupt ciliogenesis), but not by daf-6/PTCHD3 mutations (which prevent environmental exposure of sensory cilia), implying that DAF-25 functions in the cilia themselves. daf-25 encodes the C. elegans ortholog of mammalian Ankmy2, a MYND domain protein of unknown function. Disruption of DAF-25, which localizes to sensory cilia, produces no apparent cilia structure anomalies, as determined by light and electron microscopy. Hinting at its potential function, the dauer phenotype, epistatic order, and expression profile of daf-25 are similar to daf-11, which encodes a cilium-localized guanylyl cyclase. Indeed, we demonstrate that DAF-25 is required for proper DAF-11 ciliary localization. Furthermore, the functional interaction is evolutionarily conserved, as mouse Ankmy2 interacts with guanylyl cyclase GC1 from ciliary photoreceptors. The interaction may be specific because daf-25 mutants have normally-localized OSM-9/TRPV4, TAX-4/CNGA1, CHE-2/IFT80, CHE-11/IFT140, CHE-13/IFT57, BBS-8, OSM-5/IFT88, and XBX-1/D2LIC in the cilia. Intraflagellar transport (IFT) (required to build cilia) is not defective in daf-25 mutants, although the ciliary localization of DAF-25 itself is influenced in che-11 mutants, which are defective in retrograde IFT. In summary, we have discovered a novel ciliary protein that plays an important role in cGMP signaling by localizing a guanylyl cyclase to the sensory organelle.


Zdroje

1. CassadaRC

RussellRL

1975 The dauer larva, a post-embryonic developmental variant of the nematode Caenorhabditis elegans. Dev Biol 46 326 42

2. HuPJ

2007 Dauer. WormBook 1 19 doi:10.1895/wormbook.1.144.1

3. J JohnsonJF

LerouxMR

2010 cAMP and cGMP signaling: sensory systems with prokaryotic roots adopted by eukaryotic cilia. Trends Cell Biol. In press doi:10.1016/j.tcb.2010.05.005

4. BargmannCI

2006 Chemosensation in C. elegans. WormBook 1 29 doi:10.1895/wormbook.1.123.1

5. PerkinsLA

HedgecockEM

ThomsonJN

CulottiJG

1986 Mutant sensory cilia in the nematode Caenorhabditis elegans. Dev Biol 117 456 487

6. WardA

LiuJ

FengZ

XuXZS

2008 Light-sensitive neurons and channels mediate phototaxis in C. elegans. Nat Neurosci 11 916 922 doi:10.1038/nn.2155

7. BargmannCI

HartwiegE

HorvitzHR

1993 Odorant-selective genes and neurons mediate olfaction in C. elegans. Cell 74 515 527

8. InglisPN

OuG

LerouxMR

ScholeyJM

2007 The sensory cilia of Caenorhabditis elegans. WormBook 1 22 doi:10.1895/wormbook.1.126.2

9. SilvermanMA

LerouxMR

2009 Intraflagellar transport and the generation of dynamic, structurally and functionally diverse cilia. Trends Cell Biol 19 306 316 doi:10.1016/j.tcb.2009.04.002

10. SwobodaP

AdlerHT

ThomasJH

2000 The RFX-type transcription factor DAF-19 regulates sensory neuron cilium formation in C. elegans. Mol cell 5 411 21

11. BellLR

StoneS

YochemJ

ShawJE

HermanRK

2006 The molecular identities of the Caenorhabditis elegans intraflagellar transport genes dyf-6, daf-10 and osm-1. Genetics 173 1275 86

12. BirnbyDA

LinkEM

VowelsJJ

TianH

ColacurcioPL

2000 A transmembrane guanylyl cyclase (DAF-11) and Hsp90 (DAF-21) regulate a common set of chemosensory behaviors in Caenorhabditis elegans. Genetics 155 85 104

13. KimK

SatoK

ShibuyaM

ZeigerDM

ButcherRA

2009 Two Chemoreceptors Mediate Developmental Effects of Dauer Pheromone in C. elegans. Science 326 994 998

14. ZwaalRR

MendelJE

SternbergPW

PlasterkR

1997 Two Neuronal G Proteins are Involved in Chemosensation of the Caenorhabditis elegans Dauer-Inducing Pheromone. Genetics 145 715 727

15. EfimenkoE

BubbK

MakHY

HolzmanT

LerouxMR

2005 Analysis of xbx genes in C. elegans. Development 132 1923 1934 doi:10.1242/dev.01775

16. RiddleDL

SwansonMM

AlbertPS

1981 Interacting genes in nematode dauer larva formation. Nature 290 668 671

17. AlbertPS

BrownSJ

RiddleDL

1981 Sensory control of dauer larva formation in Caenorhabditis elegans. J Comp Neurol 198 435 451 doi:10.1002/cne.901980305

18. MaloneEA

ThomasJH

1994 A Screen for Nonconditional Dauer-Constitutive Mutations in Caenorhabditis elegans. Genetics 136 879 886

19. AveryL

BargmannCI

HorvitzHR

1993 The Caenorhabditis elegans unc-31 Gene Affects Multiple Nervous System-Controlled Functions. Genetics 134 455 464

20. AilionM

ThomasJH

2003 Isolation and characterization of high-temperature-induced Dauer formation mutants in Caenorhabditis elegans. Genetics 165 127 44

21. BrennerS

1974 The genetics of Caenorhabditis elegans. Genetics 77 71 94

22. KiffJE

MoermanDG

SchrieferLA

WaterstonRH

1988 Transposon-induced deletions in unc-22 of C. elegans associated with almost normal gene activity. Nature 331 631 633 doi:10.1038/331631a0

23. AntebiA

YehWH

TaitD

HedgecockEM

RiddleDL

2000 daf-12 encodes a nuclear receptor that regulates the dauer diapause and developmental age in C. elegans. Genes Dev 14 1512 1527

24. OggS

ParadisS

GottliebS

PattersonGI

LeeL

1997 The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans. Nature 389 994 999 doi:10.1038/40194

25. PattersonGI

KoweekA

WongA

LiuY

RuvkunG

1997 The DAF-3 Smad protein antagonizes TGF-beta-related receptor signaling in the Caenorhabditis elegans dauer pathway. Genes Dev 11 2679 2690

26. PerensEA

ShahamS

2005 C. elegans daf-6 encodes a patched-related protein required for lumen formation. Dev Cell 8 893 906 doi:10.1016/j.devcel.2005.03.009

27. LarsenPL

AlbertPS

RiddleDL

1995 Genes that regulate both development and longevity in Caenorhabditis elegans. Genetics 139 1567 83

28. VowelsJJ

ThomasJH

1994 Multiple chemosensory defects in daf-11 and daf-21 mutants of Caenorhabditis elegans. Genetics 138 303 316

29. StarichTA

HermanRK

KariCK

YehWH

SchackwitzWS

1995 Mutations affecting the chemosensory neurons of Caenorhabditis elegans. Genetics 139 171 188

30. WicksSR

YehRT

GishWR

WaterstonRH

PlasterkRH

2001 Rapid gene mapping in Caenorhabditis elegans using a high density polymorphism map. Nat Genet 28 160 164 doi:10.1038/88878

31. LiuY

ChenW

GaudetJ

CheneyMD

RoudaiaL

2007 Structural basis for recognition of SMRT/N-CoR by the MYND domain and its contribution to AML1/ETO's activity. Cancer Cell 11 483 497 doi:10.1016/j.ccr.2007.04.010

32. HillierLW

ReinkeV

GreenP

HirstM

MarraMA

2009 Massively parallel sequencing of the polyadenylated transcriptome of C. elegans. Genome Res 19 657 666 doi:10.1101/gr.088112.108

33. ShinH

HirstM

BainbridgeMN

MagriniV

MardisE

2008 Transcriptome analysis for Caenorhabditis elegans based on novel expressed sequence tags. BMC Biol 6 30 doi:10.1186/1741-7007-6-30

34. RogersA

AntoshechkinI

BieriT

BlasiarD

BastianiC

2008 WormBase 2007. Nucl Acids Res 36 D612 7

35. BlacqueOE

LiC

InglisPN

EsmailMA

OuG

2006 The WD Repeat-containing Protein IFTA-1 Is Required for Retrograde Intraflagellar Transport. Mol. Biol. Cell 17 5053 5062 doi:10.1091/mbc.E06-06-0571

36. OuG

KogaM

BlacqueOE

MurayamaT

OhshimaY

2007 Sensory ciliogenesis in Caenorhabditis elegans: assignment of IFT components into distinct modules based on transport and phenotypic profiles. Mol Biol Cell 18 1554 1569 doi:10.1091/mbc.E06-09-0805

37. ThomasJH

BirnbyDA

VowelsJJ

1993 Evidence for parallel processing of sensory information controlling dauer formation in Caenorhabditis elegans. Genetics 134 1105 17

38. SchaferJC

HaycraftCJ

ThomasJH

YoderBK

SwobodaP

2003 XBX-1 encodes a dynein light intermediate chain required for retrograde intraflagellar transport and cilia assembly in Caenorhabditis elegans. Mol Biol Cell 14 2057 2070 doi:10.1091/mbc.E02-10-0677

39. BlacqueOE

PerensEA

BoroevichKA

InglisPN

LiC

2005 Functional Genomics of the Cilium, a Sensory Organelle. Curr Biol 15 935 941 doi:10.1016/j.cub.2005.04.059

40. WongJP

ReboulE

MoldayRS

KastJ

2009 A Carboxy-Terminal Affinity Tag for the Purification and Mass Spectrometric Characterization of Integral Membrane Proteins. J Proteome Res 8 2388 2396 doi:10.1021/pr801008c

41. SharmaN

BerbariNF

YoderBK

2008 Ciliary dysfunction in developmental abnormalities and diseases. Curr Top Dev Biol 85 371 427 doi:10.1016/S0070-2153(08)00813-2

42. LancasterMA

GleesonJG

2009 The primary cilium as a cellular signaling center: lessons from disease. Curr Opin Genet Dev 19 220 229 doi:10.1016/j.gde.2009.04.008

43. KitiratschkyVBD

WilkeR

RennerAB

KellnerU

VadalàM

2008 Mutation analysis identifies GUCY2D as the major gene responsible for autosomal dominant progressive cone degeneration. Invest Ophthalmol Vis Sci 49 5015 5023 doi:10.1167/iovs.08-1901

44. HaiderNB

MollemaN

GauleM

YuanY

SachsAJ

2009 Nr2e3-directed transcriptional regulation of genes involved in photoreceptor development and cell-type specific phototransduction. Exp Eye Res 89 365 372

45. FujiwaraM

SenguptaP

McIntireSL

2002 Regulation of Body Size and Behavioral State of C. elegans by Sensory Perception and the EGL-4 cGMP-Dependent Protein Kinase. Neuron 36 1091 1102 doi:10.1016/S0896-6273(02)01093-0

46. WenselTG

2008 Signal transducing membrane complexes of photoreceptor outer segments. Vision Res 48 2052 2061 doi:10.1016/j.visres.2008.03.010

47. MaydanJS

OkadaHM

FlibotteS

EdgleyML

MoermanDG

2009 De Novo identification of single nucleotide mutations in Caenorhabditis elegans using array comparative genomic hybridization. Genetics 181 1673 1677 doi:10.1534/genetics.108.100065

48. SaekiS

YamamotoM

IinoY

2001 Plasticity of chemotaxis revealed by paired presentation of a chemoattractant and starvation in the nematode Caenorhabditis elegans. J Exp Biol 204 1757 1764

49. EvansT

2006 Transformation and microinjection. WormBook. doi/10.1895/ wormbook.1.108.1

50. SnowJJ

OuG

GunnarsonAL

WalkerMRS

ZhouHM

2004 Two anterograde intraflagellar transport motors cooperate to build sensory cilia on C. elegans neurons. Nat Cell Biol 6 1109 1113 doi:10.1038/ncb1186

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2010 Číslo 11
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#