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Conserved Genes Act as Modifiers of Invertebrate SMN Loss of Function Defects


Spinal Muscular Atrophy (SMA) is caused by diminished function of the Survival of Motor Neuron (SMN) protein, but the molecular pathways critical for SMA pathology remain elusive. We have used genetic approaches in invertebrate models to identify conserved SMN loss of function modifier genes. Drosophila melanogaster and Caenorhabditis elegans each have a single gene encoding a protein orthologous to human SMN; diminished function of these invertebrate genes causes lethality and neuromuscular defects. To find genes that modulate SMN function defects across species, two approaches were used. First, a genome-wide RNAi screen for C. elegans SMN modifier genes was undertaken, yielding four genes. Second, we tested the conservation of modifier gene function across species; genes identified in one invertebrate model were tested for function in the other invertebrate model. Drosophila orthologs of two genes, which were identified originally in C. elegans, modified Drosophila SMN loss of function defects. C. elegans orthologs of twelve genes, which were originally identified in a previous Drosophila screen, modified C. elegans SMN loss of function defects. Bioinformatic analysis of the conserved, cross-species, modifier genes suggests that conserved cellular pathways, specifically endocytosis and mRNA regulation, act as critical genetic modifiers of SMN loss of function defects across species.


Vyšlo v časopise: Conserved Genes Act as Modifiers of Invertebrate SMN Loss of Function Defects. PLoS Genet 6(10): e32767. doi:10.1371/journal.pgen.1001172
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1001172

Souhrn

Spinal Muscular Atrophy (SMA) is caused by diminished function of the Survival of Motor Neuron (SMN) protein, but the molecular pathways critical for SMA pathology remain elusive. We have used genetic approaches in invertebrate models to identify conserved SMN loss of function modifier genes. Drosophila melanogaster and Caenorhabditis elegans each have a single gene encoding a protein orthologous to human SMN; diminished function of these invertebrate genes causes lethality and neuromuscular defects. To find genes that modulate SMN function defects across species, two approaches were used. First, a genome-wide RNAi screen for C. elegans SMN modifier genes was undertaken, yielding four genes. Second, we tested the conservation of modifier gene function across species; genes identified in one invertebrate model were tested for function in the other invertebrate model. Drosophila orthologs of two genes, which were identified originally in C. elegans, modified Drosophila SMN loss of function defects. C. elegans orthologs of twelve genes, which were originally identified in a previous Drosophila screen, modified C. elegans SMN loss of function defects. Bioinformatic analysis of the conserved, cross-species, modifier genes suggests that conserved cellular pathways, specifically endocytosis and mRNA regulation, act as critical genetic modifiers of SMN loss of function defects across species.


Zdroje

1. LefebvreS

BurglenL

ReboulletS

ClermontO

BurletP

1995 Identification and characterization of a spinal muscular atrophy-determining gene. Cell 80 155 165

2. BodaB

MasC

GiudicelliC

NepoteV

GuimiotF

2004 Survival motor neuron SMN1 and SMN2 gene promoters: identical sequences and differential expression in neurons and non-neuronal cells. Eur J Hum Genet 12 729 737

3. MonaniUR

McPhersonJD

BurghesAH

1999 Promoter analysis of the human centromeric and telomeric survival motor neuron genes (SMNC and SMNT). Biochim Biophys Acta 1445 330 336

4. PearnJ

1980 Classification of spinal muscular atrophies. Lancet 1 919 922

5. CusinV

ClermontO

GerardB

ChantereauD

ElionJ

2003 Prevalence of SMN1 deletion and duplication in carrier and normal populations: implication for genetic counselling. J Med Genet 40 e39

6. McAndrewPE

ParsonsDW

SimardLR

RochetteC

RayPN

1997 Identification of proximal spinal muscular atrophy carriers and patients by analysis of SMNT and SMNC gene copy number. Am J Hum Genet 60 1411 1422

7. OginoS

LeonardDG

RennertH

EwensWJ

WilsonRB

2002 Genetic risk assessment in carrier testing for spinal muscular atrophy. Am J Med Genet 110 301 307

8. GubitzAK

FengW

DreyfussG

2004 The SMN complex. Exp Cell Res 296 51 56

9. OhnT

KedershaN

HickmanT

TisdaleS

AndersonP

2008 A functional RNAi screen links O-GlcNAc modification of ribosomal proteins to stress granule and processing body assembly. Nat Cell Biol 10 1224 1231

10. HuaY

ZhouJ

2004 Survival motor neuron protein facilitates assembly of stress granules. FEBS Lett 572 69 74

11. FanL

SimardLR

2002 Survival motor neuron (SMN) protein: role in neurite outgrowth and neuromuscular maturation during neuronal differentiation and development. Hum Mol Genet 11 1605 1614

12. RossollW

JablonkaS

AndreassiC

KroningAK

KarleK

2003 Smn, the spinal muscular atrophy-determining gene product, modulates axon growth and localization of beta-actin mRNA in growth cones of motoneurons. J Cell Biol 163 801 812

13. FrancisJW

SandrockAW

BhidePG

VonsattelJP

BrownRHJr

1998 Heterogeneity of subcellular localization and electrophoretic mobility of survival motor neuron (SMN) protein in mammalian neural cells and tissues. Proc Natl Acad Sci U S A 95 6492 6497

14. GiavazziA

SetolaV

SimonatiA

BattagliaG

2006 Neuronal-specific roles of the survival motor neuron protein: evidence from survival motor neuron expression patterns in the developing human central nervous system. J Neuropathol Exp Neurol 65 267 277

15. PagliardiniS

GiavazziA

SetolaV

LizierC

Di LucaM

2000 Subcellular localization and axonal transport of the survival motor neuron (SMN) protein in the developing rat spinal cord. Hum Mol Genet 9 47 56

16. GennarelliM

LucarelliM

CaponF

PizzutiA

MerliniL

1995 Survival motor neuron gene transcript analysis in muscles from spinal muscular atrophy patients. Biochem Biophys Res Commun 213 342 348

17. CoovertDD

LeTT

McAndrewPE

StrasswimmerJ

CrawfordTO

1997 The survival motor neuron protein in spinal muscular atrophy. Hum Mol Genet 6 1205 1214

18. RajendraTK

GonsalvezGB

WalkerMP

ShpargelKB

SalzHK

2007 A Drosophila melanogaster model of spinal muscular atrophy reveals a function for SMN in striated muscle. J Cell Biol 176 831 841

19. WalkerMP

RajendraTK

SaievaL

FuentesJL

PellizzoniL

2008 The SMN complex localizes to the sarcomeric Z-disc and is a proteolytic target of calpain. Hum Mol Genet

20. MourelatosZ

DostieJ

PaushkinS

SharmaA

CharrouxB

2002 miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs. Genes Dev 16 720 728

21. PellizzoniL

BacconJ

CharrouxB

DreyfussG

2001 The survival of motor neurons (SMN) protein interacts with the snoRNP proteins fibrillarin and GAR1. Curr Biol 11 1079 1088

22. WhiteheadSE

JonesKW

ZhangX

ChengX

TernsRM

2002 Determinants of the interaction of the spinal muscular atrophy disease protein SMN with the dimethylarginine-modified box H/ACA small nucleolar ribonucleoprotein GAR1. J Biol Chem 277 48087 48093

23. Cifuentes-DiazC

FrugierT

TizianoFD

LaceneE

RoblotN

2001 Deletion of murine SMN exon 7 directed to skeletal muscle leads to severe muscular dystrophy. J Cell Biol 152 1107 1114

24. ShafeyD

CotePD

KotharyR

2005 Hypomorphic Smn knockdown C2C12 myoblasts reveal intrinsic defects in myoblast fusion and myotube morphology. Exp Cell Res 311 49 61

25. ChanYB

Miguel-AliagaI

FranksC

ThomasN

TrulzschB

2003 Neuromuscular defects in a Drosophila survival motor neuron gene mutant. Hum Mol Genet 12 1367 1376

26. ChangHC

DimlichDN

YokokuraT

MukherjeeA

KankelMW

2008 Modeling spinal muscular atrophy in Drosophila. PLoS ONE 3 e3209 doi:10.1371/journal.pone.0003209

27. McWhorterML

MonaniUR

BurghesAH

BeattieCE

2003 Knockdown of the survival motor neuron (Smn) protein in zebrafish causes defects in motor axon outgrowth and pathfinding. J Cell Biol 162 919 931

28. KariyaS

ParkGH

Maeno-HikichiY

LeykekhmanO

LutzC

2008 Reduced SMN protein impairs maturation of the neuromuscular junctions in mouse models of spinal muscular atrophy. Hum Mol Genet 17 2552 2569

29. LorsonCL

AndrophyEJ

2000 An exonic enhancer is required for inclusion of an essential exon in the SMA-determining gene SMN. Hum Mol Genet 9 259 265

30. MonaniUR

CoovertDD

BurghesAH

2000 Animal models of spinal muscular atrophy. Hum Mol Genet 9 2451 2457

31. MonaniUR

LorsonCL

ParsonsDW

PriorTW

AndrophyEJ

1999 A single nucleotide difference that alters splicing patterns distinguishes the SMA gene SMN1 from the copy gene SMN2. Hum Mol Genet 8 1177 1183

32. LefebvreS

BurletP

LiuQ

BertrandyS

ClermontO

1997 Correlation between severity and SMN protein level in spinal muscular atrophy. Nat Genet 16 265 269

33. FeldkotterM

SchwarzerV

WirthR

WienkerTF

WirthB

2002 Quantitative analyses of SMN1 and SMN2 based on real-time lightCycler PCR: fast and highly reliable carrier testing and prediction of severity of spinal muscular atrophy. Am J Hum Genet 70 358 368

34. WirthB

HerzM

WetterA

MoskauS

HahnenE

1999 Quantitative analysis of survival motor neuron copies: identification of subtle SMN1 mutations in patients with spinal muscular atrophy, genotype-phenotype correlation, and implications for genetic counseling. Am J Hum Genet 64 1340 1356

35. LefebvreS

BurglenL

FrezalJ

MunnichA

MelkiJ

1998 The role of the SMN gene in proximal spinal muscular atrophy. Hum Mol Genet 7 1531 1536

36. BurghesAH

1997 When is a deletion not a deletion? When it is converted. Am J Hum Genet 61 9 15

37. OpreaGE

KroberS

McWhorterML

RossollW

MullerS

2008 Plastin 3 is a protective modifier of autosomal recessive spinal muscular atrophy. Science 320 524 527

38. BretscherA

1981 Fimbrin is a cytoskeletal protein that crosslinks F-actin in vitro. Proc Natl Acad Sci U S A 78 6849 6853

39. BretscherA

WeberK

1980 Fimbrin, a new microfilament-associated protein present in microvilli and other cell surface structures. J Cell Biol 86 335 340

40. GlenneyJRJr

KaulfusP

MatsudairaP

WeberK

1981 F-actin binding and bundling properties of fimbrin, a major cytoskeletal protein of microvillus core filaments. J Biol Chem 256 9283 9288

41. AdamsAE

BotsteinD

DrubinDG

1989 A yeast actin-binding protein is encoded by SAC6, a gene found by suppression of an actin mutation. Science 243 231 233

42. KublerE

RiezmanH

1993 Actin and fimbrin are required for the internalization step of endocytosis in yeast. EMBO J 12 2855 2862

43. BowermanM

AndersonCL

BeauvaisA

BoylPP

WitkeW

2009 SMN, profilin IIa and plastin 3: a link between the deregulation of actin dynamics and SMA pathogenesis. Mol Cell Neurosci 42 66 74

44. BrieseM

EsmaeiliB

FrabouletS

BurtEC

ChristodoulouS

2009 Deletion of smn-1, the Caenorhabditis elegans ortholog of the spinal muscular atrophy gene, results in locomotor dysfunction and reduced lifespan. Hum Mol Genet 18 97 104

45. Miguel-AliagaI

CulettoE

WalkerDS

BaylisHA

SattelleDB

1999 The Caenorhabditis elegans orthologue of the human gene responsible for spinal muscular atrophy is a maternal product critical for germline maturation and embryonic viability. Hum Mol Genet 8 2133 2143

46. McKimKS

PetersK

RoseAM

1993 Two types of sites required for meiotic chromosome pairing in Caenorhabditis elegans. Genetics 134 749 768

47. TimmonsL

FireA

1998 Specific interference by ingested dsRNA. Nature 395 854

48. KamathRS

Martinez-CamposM

ZipperlenP

FraserAG

AhringerJ

2001 Effectiveness of specific RNA-mediated interference through ingested double-stranded RNA in Caenorhabditis elegans. Genome Biol 2 RESEARCH0002

49. TimmonsL

CourtDL

FireA

2001 Ingestion of bacterially expressed dsRNAs can produce specific and potent genetic interference in Caenorhabditis elegans. Gene 263 103 112

50. RualJF

CeronJ

KorethJ

HaoT

NicotAS

2004 Toward improving Caenorhabditis elegans phenome mapping with an ORFeome-based RNAi library. Genome Res 14 2162 2168

51. PulakR

2006 Techniques for analysis, sorting, and dispensing of C. elegans on the COPAS flow-sorting system. Methods Mol Biol 351 275 286

52. HuangLS

SternbergPW

2006 Genetic dissection of developmental pathways. WormBook 1 19

53. KamathRS

AhringerJ

2003 Genome-wide RNAi screening in Caenorhabditis elegans. Methods 30 313 321

54. LallS

PianoF

DavisRE

2005 Caenorhabditis elegans decapping proteins: localization and functional analysis of Dcp1, Dcp2, and DcpS during embryogenesis. Mol Biol Cell 16 5880 5890

55. AveryL

1993 The genetics of feeding in Caenorhabditis elegans. Genetics 133 897 917

56. SulstonJE

HorvitzHR

1977 Post-embryonic cell lineages of the nematode, Caenorhabditis elegans. Dev Biol 56 110 156

57. SulstonJE

SchierenbergE

WhiteJG

ThomsonJN

1983 The embryonic cell lineage of the nematode Caenorhabditis elegans. Dev Biol 100 64 119

58. SimmerF

MoormanC

van der LindenAM

KuijkE

van den BerghePV

2003 Genome-wide RNAi of C. elegans using the hypersensitive rrf-3 strain reveals novel gene functions. PLoS Biol 1 e12 doi:10.1371/journal.pbio.0000012

59. KennedyS

WangD

RuvkunG

2004 A conserved siRNA-degrading RNase negatively regulates RNA interference in C. elegans. Nature 427 645 649

60. FukutoHS

FerkeyDM

ApicellaAJ

LansH

SharmeenT

2004 G protein-coupled receptor kinase function is essential for chemosensation in C. elegans. Neuron 42 581 593

61. BarrettPL

FlemingJT

GobelV

2004 Targeted gene alteration in Caenorhabditis elegans by gene conversion. Nat Genet 36 1231 1237

62. Gengyo-AndoK

MitaniS

2000 Characterization of mutations induced by ethyl methanesulfonate, UV, and trimethylpsoralen in the nematode Caenorhabditis elegans. Biochem Biophys Res Commun 269 64 69

63. GilchristEJ

O'NeilNJ

RoseAM

ZetkaMC

HaughnGW

2006 TILLING is an effective reverse genetics technique for Caenorhabditis elegans. BMC Genomics 7 262

64. JansenG

HazendonkE

ThijssenKL

PlasterkRH

1997 Reverse genetics by chemical mutagenesis in Caenorhabditis elegans. Nat Genet 17 119 121

65. LesaGM

2006 Isolation of Caenorhabditis elegans gene knockouts by PCR screening of chemically mutagenized libraries. Nat Protoc 1 2231 2240

66. LiuT

KimK

LiC

BarrMM

2007 FMRFamide-like neuropeptides and mechanosensory touch receptor neurons regulate male sexual turning behavior in Caenorhabditis elegans. J Neurosci 27 7174 7182

67. LiC

KimK

2008 Neuropeptides. WormBook 1 36

68. MountSM

SalzHK

2000 Pre-messenger RNA processing factors in the Drosophila genome. J Cell Biol 150 F37 44

69. LaskoP

2000 The Drosophila melanogaster genome: translation factors and RNA binding proteins. J Cell Biol 150 F51 56

70. NambuJR

Murphy-ErdoshC

AndrewsPC

FeistnerGJ

SchellerRH

1988 Isolation and characterization of a Drosophila neuropeptide gene. Neuron 1 55 61

71. RoulierEM

FyrbergC

FyrbergE

1992 Perturbations of Drosophila alpha-actinin cause muscle paralysis, weakness, and atrophy but do not confer obvious nonmuscle phenotypes. J Cell Biol 116 911 922

72. FyrbergE

KellyM

BallE

FyrbergC

ReedyMC

1990 Molecular genetics of Drosophila alpha-actinin: mutant alleles disrupt Z disc integrity and muscle insertions. J Cell Biol 110 1999 2011

73. InoueT

ThomasJH

2000 Targets of TGF-beta signaling in Caenorhabditis elegans dauer formation. Dev Biol 217 192 204

74. BrundageL

AveryL

KatzA

KimUJ

MendelJE

1996 Mutations in a C. elegans Gqalpha gene disrupt movement, egg laying, and viability. Neuron 16 999 1009

75. GkogkasC

MiddletonS

KremerAM

WardropeC

HannahM

2008 VAPB interacts with and modulates the activity of ATF6. Hum Mol Genet 17 1517 1526

76. WangH

WuLJ

KimSS

LeeFJ

GongB

2008 FMRP acts as a key messenger for dopamine modulation in the forebrain. Neuron 59 634 647

77. PiazzonN

RageF

SchlotterF

MoineH

BranlantC

2008 In vitro and in cellulo evidences for association of the survival of motor neuron complex with the fragile X mental retardation protein. J Biol Chem 283 5598 5610

78. BauerPO

NukinaN

2009 The pathogenic mechanisms of polyglutamine diseases and current therapeutic strategies. J Neurochem 110 1737 1765

79. CrawfordTO

PardoCA

1996 The neurobiology of childhood spinal muscular atrophy. Neurobiol Dis 3 97 110

80. GoedertM

SpillantiniMG

2006 A century of Alzheimer's disease. Science 314 777 781

81. LangAE

LozanoAM

1998 Parkinson's disease. First of two parts. N Engl J Med 339 1044 1053

82. JorgensenEM

MangoSE

2002 The art and design of genetic screens: Caenorhabditis elegans. Nat Rev Genet 3 356 369

83. DimitriadiM

HartAC

2010 Neurodegenerative disorders: Insights from the nematode Caenorhabditis elegans. Neurobiol Dis

84. FiuzaUM

AriasAM

2007 Cell and molecular biology of Notch. J Endocrinol 194 459 474

85. KimSK

2007 Common aging pathways in worms, flies, mice and humans. J Exp Biol 210 1607 1612

86. LeichtDT

BalanV

KaplunA

Singh-GuptaV

KaplunL

2007 Raf kinases: function, regulation and role in human cancer. Biochim Biophys Acta 1773 1196 1212

87. SchlegelA

StainierDY

2007 Lessons from “lower” organisms: what worms, flies, and zebrafish can teach us about human energy metabolism. PLoS Genet 3 e199 doi:10.1371/journal.pgen.0030199

88. SilvermanGA

LukeCJ

BhatiaSR

LongOS

VeticaAC

2009 Modeling molecular and cellular aspects of human disease using the nematode Caenorhabditis elegans. Pediatr Res 65 10 18

89. KaksonenM

ToretCP

DrubinDG

2005 A modular design for the clathrin- and actin-mediated endocytosis machinery. Cell 123 305 320

90. RalserM

NonhoffU

AlbrechtM

LengauerT

WankerEE

2005 Ataxin-2 and huntingtin interact with endophilin-A complexes to function in plastin-associated pathways. Hum Mol Genet 14 2893 2909

91. Singer-KrugerB

NemotoY

DaniellL

Ferro-NovickS

De CamilliP

1998 Synaptojanin family members are implicated in endocytic membrane traffic in yeast. J Cell Sci 111 ( Pt 22) 3347 3356

92. GibbingsDJ

CiaudoC

ErhardtM

VoinnetO

2009 Multivesicular bodies associate with components of miRNA effector complexes and modulate miRNA activity. Nat Cell Biol 11 1143 1149

93. LeeYS

PressmanS

AndressAP

KimK

WhiteJL

2009 Silencing by small RNAs is linked to endosomal trafficking. Nat Cell Biol 11 1150 1156

94. KongL

WangX

ChoeDW

PolleyM

BurnettBG

2009 Impaired synaptic vesicle release and immaturity of neuromuscular junctions in spinal muscular atrophy mice. J Neurosci 29 842 851

95. BrennerS

1974 The genetics of Caenorhabditis elegans. Genetics 77 71 94

96. BeanCJ

SchanerCE

KellyWG

2004 Meiotic pairing and imprinted X chromatin assembly in Caenorhabditis elegans. Nat Genet 36 100 105

97. BilinskiSM

JaglarzMK

SzymanskaB

EtkinLD

KlocM

2004 Sm proteins, the constituents of the spliceosome, are components of nuage and mitochondrial cement in Xenopus oocytes. Exp Cell Res 299 171 178

98. DostieJ

MourelatosZ

YangM

SharmaA

DreyfussG

2003 Numerous microRNPs in neuronal cells containing novel microRNAs. RNA 9 180 186

99. HillierLW

ReinkeV

GreenP

HirstM

MarraMA

2009 Massively parallel sequencing of the polyadenylated transcriptome of C. elegans. Genome Res 19 657 666

100. TownendJ

2002 Practical statistics for environmental and biological scientists Chichester, UK John Wiley and Sons Ltd

101. GunawardenaS

GoldsteinLS

2001 Disruption of axonal transport and neuronal viability by amyloid precursor protein mutations in Drosophila. Neuron 32 389 401

102. CaoYJ

DreixlerJC

CoueyJJ

HouamedKM

2002 Modulation of recombinant and native neuronal SK channels by the neuroprotective drug riluzole. Eur J Pharmacol 449 47 54

103. BensimonG

LacomblezL

MeiningerV

1994 A controlled trial of riluzole in amyotrophic lateral sclerosis. ALS/Riluzole Study Group. N Engl J Med 330 585 591

104. CouratierP

SindouP

EsclaireF

LouvelE

HugonJ

1994 Neuroprotective effects of riluzole in ALS CSF toxicity. Neuroreport 5 1012 1014

105. HaddadH

Cifuentes-DiazC

MiroglioA

RoblotN

JoshiV

2003 Riluzole attenuates spinal muscular atrophy disease progression in a mouse model. Muscle Nerve 28 432 437

106. NishimuraAL

Mitne-NetoM

SilvaHC

Richieri-CostaA

MiddletonS

2004 A mutation in the vesicle-trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis. Am J Hum Genet 75 822 831

107. ShenV

LiuH

LiuSW

JiaoX

KiledjianM

2008 DcpS scavenger decapping enzyme can modulate pre-mRNA splicing. RNA 14 1132 1142

108. SinghJ

SalciusM

LiuSW

StakerBL

MishraR

2008 DcpS as a therapeutic target for spinal muscular atrophy. ACS Chem Biol 3 711 722

109. NonisD

SchmidtMH

van de LooS

EichF

DikicI

2008 Ataxin-2 associates with the endocytosis complex and affects EGF receptor trafficking. Cell Signal 20 1725 1739

110. LimJ

HaoT

ShawC

PatelAJ

SzaboG

2006 A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration. Cell 125 801 814

111. LiS

ArmstrongCM

BertinN

GeH

MilsteinS

2004 A map of the interactome network of the metazoan C. elegans. Science 303 540 543

112. JeongH

ThenF

MeliaTJJr

MazzulliJR

CuiL

2009 Acetylation targets mutant huntingtin to autophagosomes for degradation. Cell 137 60 72

113. JiaK

HartAC

LevineB

2007 Autophagy genes protect against disease caused by polyglutamine expansion proteins in Caenorhabditis elegans. Autophagy 3 21 25

114. SerraHG

DuvickL

ZuT

CarlsonK

StevensS

2006 RORalpha-mediated Purkinje cell development determines disease severity in adult SCA1 mice. Cell 127 697 708

115. PetrelliA

GilestroGF

LanzardoS

ComoglioPM

MigoneN

2002 The endophilin-CIN85-Cbl complex mediates ligand-dependent downregulation of c-Met. Nature 416 187 190

116. KanekoT

MaedaA

TakefujiM

AoyamaH

NakayamaM

2005 Rho mediates endocytosis of epidermal growth factor receptor through phosphorylation of endophilin A1 by Rho-kinase. Genes Cells 10 973 987

117. GuillaumondF

DardenteH

GiguereV

CermakianN

2005 Differential control of Bmal1 circadian transcription by REV-ERB and ROR nuclear receptors. J Biol Rhythms 20 391 403

118. FormanBM

ChenJ

BlumbergB

KliewerSA

HenshawR

1994 Cross-talk among ROR alpha 1 and the Rev-erb family of orphan nuclear receptors. Mol Endocrinol 8 1253 1261

119. FreemanJL

PitcherJA

LiX

BennettV

LefkowitzRJ

2000 alpha-Actinin is a potent regulator of G protein-coupled receptor kinase activity and substrate specificity in vitro. FEBS Lett 473 280 284

120. Chatellard-CausseC

BlotB

CristinaN

TorchS

MissottenM

2002 Alix (ALG-2-interacting protein X), a protein involved in apoptosis, binds to endophilins and induces cytoplasmic vacuolization. J Biol Chem 277 29108 29115

121. LuL

ZhangQ

TimofeyevV

ZhangZ

YoungJN

2007 Molecular coupling of a Ca2+-activated K+ channel to L-type Ca2+ channels via alpha-actinin2. Circ Res 100 112 120

122. ChenB

BorinsteinSC

GillisJ

SykesVW

BoglerO

2000 The glioma-associated protein SETA interacts with AIP1/Alix and ALG-2 and modulates apoptosis in astrocytes. J Biol Chem 275 19275 19281

123. SchmidtMH

HoellerD

YuJ

FurnariFB

CaveneeWK

2004 Alix/AIP1 antagonizes epidermal growth factor receptor downregulation by the Cbl-SETA/CIN85 complex. Mol Cell Biol 24 8981 8993

124. CarmanCV

LisantiMP

BenovicJL

1999 Regulation of G protein-coupled receptor kinases by caveolin. J Biol Chem 274 8858 8864

125. RalserM

AlbrechtM

NonhoffU

LengauerT

LehrachH

2005 An integrative approach to gain insights into the cellular function of human ataxin-2. J Mol Biol 346 203 214

126. LessingD

BoniniNM

2008 Polyglutamine genes interact to modulate the severity and progression of neurodegeneration in Drosophila. PLoS Biol 6 e29 doi:10.1371/journal.pbio.0060029

127. CioskR

DePalmaM

PriessJR

2004 ATX-2, the C. elegans ortholog of ataxin 2, functions in translational regulation in the germline. Development 131 4831 4841

128. SatterfieldTF

PallanckLJ

2006 Ataxin-2 and its Drosophila homolog, ATX2, physically assemble with polyribosomes. Hum Mol Genet 15 2523 2532

129. NonhoffU

RalserM

WelzelF

PicciniI

BalzereitD

2007 Ataxin-2 interacts with the DEAD/H-box RNA helicase DDX6 and interferes with P-bodies and stress granules. Mol Biol Cell 18 1385 1396

130. KozlovG

TrempeJF

KhaleghpourK

KahvejianA

EkielI

2001 Structure and function of the C-terminal PABC domain of human poly(A)-binding protein. Proc Natl Acad Sci U S A 98 4409 4413

131. IkezuT

TrappBD

SongKS

SchlegelA

LisantiMP

1998 Caveolae, plasma membrane microdomains for alpha-secretase-mediated processing of the amyloid precursor protein. J Biol Chem 273 10485 10495

132. MassenetS

PellizzoniL

PaushkinS

MattajIW

DreyfussG

2002 The SMN complex is associated with snRNPs throughout their cytoplasmic assembly pathway. Mol Cell Biol 22 6533 6541

133. GareusR

Di NardoA

RybinV

WitkeW

2006 Mouse profilin 2 regulates endocytosis and competes with SH3 ligand binding to dynamin 1. J Biol Chem 281 2803 2811

134. SchaferDA

WeedSA

BinnsD

KarginovAV

ParsonsJT

2002 Dynamin2 and cortactin regulate actin assembly and filament organization. Curr Biol 12 1852 1857

135. WitkeW

PodtelejnikovAV

Di NardoA

SutherlandJD

GurniakCB

1998 In mouse brain profilin I and profilin II associate with regulators of the endocytic pathway and actin assembly. EMBO J 17 967 976

136. Al-RamahiI

PerezAM

LimJ

ZhangM

SorensenR

2007 dAtaxin-2 mediates expanded Ataxin-1-induced neurodegeneration in a Drosophila model of SCA1. PLoS Genet 3 e234 doi:10.1371/journal.pgen.0030234

137. Ghosh-RoyA

DesaiBS

RayK

2005 Dynein light chain 1 regulates dynamin-mediated F-actin assembly during sperm individualization in Drosophila. Mol Biol Cell 16 3107 3116

138. Navarro-LeridaI

Martinez MorenoM

RoncalF

GavilanesF

AlbarJP

2004 Proteomic identification of brain proteins that interact with dynein light chain LC8. Proteomics 4 339 346

139. PanS

WangR

ZhouX

HeG

KoomenJ

2006 Involvement of the conserved adaptor protein Alix in actin cytoskeleton assembly. J Biol Chem 281 34640 34650

140. GaillardS

BartoliM

CastetsF

MonneronA

2001 Striatin, a calmodulin-dependent scaffolding protein, directly binds caveolin-1. FEBS Lett 508 49 52

141. KhandjianEW

HuotME

TremblayS

DavidovicL

MazrouiR

2004 Biochemical evidence for the association of fragile X mental retardation protein with brain polyribosomal ribonucleoparticles. Proc Natl Acad Sci U S A 101 13357 13362

142. GagneJP

BonicalziME

GagneP

OuelletME

HendzelMJ

2005 Poly(ADP-ribose) glycohydrolase is a component of the FMRP-associated messenger ribonucleoparticles. Biochem J 392 499 509

143. CastetsF

BartoliM

BarnierJV

BaillatG

SalinP

1996 A novel calmodulin-binding protein, belonging to the WD-repeat family, is localized in dendrites of a subset of CNS neurons. J Cell Biol 134 1051 1062

144. ShaoJ

WelchWJ

DiprosperoNA

DiamondMI

2008 Phosphorylation of profilin by ROCK1 regulates polyglutamine aggregation. Mol Cell Biol 28 5196 5208

145. BaillatG

GaillardS

CastetsF

MonneronA

2002 Interactions of phocein with nucleoside-diphosphate kinase, Eps15, and Dynamin I. J Biol Chem 277 18961 18966

146. SittlerA

WalterS

WedemeyerN

HasenbankR

ScherzingerE

1998 SH3GL3 associates with the Huntingtin exon 1 protein and promotes the formation of polygln-containing protein aggregates. Mol Cell 2 427 436

147. QinZH

WangY

SappE

CuiffoB

WankerE

2004 Huntingtin bodies sequester vesicle-associated proteins by a polyproline-dependent interaction. J Neurosci 24 269 281

148. FallonL

BelangerCM

CoreraAT

KontogianneaM

Regan-KlapiszE

2006 A regulated interaction with the UIM protein Eps15 implicates parkin in EGF receptor trafficking and PI(3)K-Akt signalling. Nat Cell Biol 8 834 842

149. SalciniAE

HilliardMA

CroceA

ArbucciS

LuzziP

2001 The Eps15 C. elegans homologue EHS-1 is implicated in synaptic vesicle recycling. Nat Cell Biol 3 755 760

150. KrishnanKS

RikhyR

RaoS

ShivalkarM

MoskoM

2001 Nucleoside diphosphate kinase, a source of GTP, is required for dynamin-dependent synaptic vesicle recycling. Neuron 30 197 210

151. SharmaA

LambrechtsA

Hao leT

LeTT

SewryCA

2005 A role for complexes of survival of motor neurons (SMN) protein with gemins and profilin in neurite-like cytoplasmic extensions of cultured nerve cells. Exp Cell Res 309 185 197

152. GiesemannT

Rathke-HartliebS

RothkegelM

BartschJW

BuchmeierS

1999 A role for polyproline motifs in the spinal muscular atrophy protein SMN. Profilins bind to and colocalize with smn in nuclear gems. J Biol Chem 274 37908 37914

153. BowermanM

ShafeyD

KotharyR

2007 Smn depletion alters profilin II expression and leads to upregulation of the RhoA/ROCK pathway and defects in neuronal integrity. J Mol Neurosci 32 120 131

154. ReeveSP

BassettoL

GenovaGK

KleynerY

LeyssenM

2005 The Drosophila fragile X mental retardation protein controls actin dynamics by directly regulating profilin in the brain. Curr Biol 15 1156 1163

155. TessierCR

BroadieK

2008 Drosophila fragile X mental retardation protein developmentally regulates activity-dependent axon pruning. Development 135 1547 1557

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PLOS Genetics


2010 Číslo 10
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