#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Syd/JIP3 and JNK Signaling Are Required for Myonuclear Positioning and Muscle Function


A common pathology found in numerous cases of muscle diseases, including congenital myopathies and muscular dystrophies, is aberrantly located nuclei within individual multinucleated muscle cells. However, whether or not mispositioned myonuclei are a cause or consequence of muscle disease states is currently debated. Here, we take advantage of the model organism, Drosophila melanogaster, which shares the conserved myofiber found in mammalian systems, to identify Syd as a novel regulator of myonuclear positioning. We show that Syd is responsible for mediating the activities of Kinesin and Dynein, two motor proteins that exert forces to pull myonuclei into place. Moreover, we demonstrate that Syd-dependent myonuclear positioning also requires intracellular signaling from the JNK MAPK cascade to direct when and how myonuclei are moved into proper position. This work thus identifies developmental cues that direct proper muscle morphogenesis, suggesting that cases of muscle disease may result from a failure to achieve initial spacing of myonuclei. Supporting this notion, we find that loss of Syd impairs muscle function, but resupplying Syd restores proper myonuclear spacing and muscle function. These findings are particularly important as mispositioned myonuclei gain traction as a potential contributing factor in cases of muscle disease.


Vyšlo v časopise: Syd/JIP3 and JNK Signaling Are Required for Myonuclear Positioning and Muscle Function. PLoS Genet 10(12): e32767. doi:10.1371/journal.pgen.1004880
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004880

Souhrn

A common pathology found in numerous cases of muscle diseases, including congenital myopathies and muscular dystrophies, is aberrantly located nuclei within individual multinucleated muscle cells. However, whether or not mispositioned myonuclei are a cause or consequence of muscle disease states is currently debated. Here, we take advantage of the model organism, Drosophila melanogaster, which shares the conserved myofiber found in mammalian systems, to identify Syd as a novel regulator of myonuclear positioning. We show that Syd is responsible for mediating the activities of Kinesin and Dynein, two motor proteins that exert forces to pull myonuclei into place. Moreover, we demonstrate that Syd-dependent myonuclear positioning also requires intracellular signaling from the JNK MAPK cascade to direct when and how myonuclei are moved into proper position. This work thus identifies developmental cues that direct proper muscle morphogenesis, suggesting that cases of muscle disease may result from a failure to achieve initial spacing of myonuclei. Supporting this notion, we find that loss of Syd impairs muscle function, but resupplying Syd restores proper myonuclear spacing and muscle function. These findings are particularly important as mispositioned myonuclei gain traction as a potential contributing factor in cases of muscle disease.


Zdroje

1. RomeroNB (2010) Centronuclear myopathies: a widening concept. Neuromuscul Disord 20: 223–228.

2. JeannetPY, BassezG, EymardB, LaforetP, UrtizbereaJA, et al. (2004) Clinical and histologic findings in autosomal centronuclear myopathy. Neurology 62: 1484–1490.

3. PuckelwartzMJ, KesslerE, ZhangY, HodzicD, RandlesKN, et al. (2009) Disruption of nesprin-1 produces an Emery Dreifuss muscular dystrophy-like phenotype in mice. Hum Mol Genet 18: 607–620.

4. MetzgerT, GacheV, XuM, CadotB, FolkerES, et al. (2012) MAP and kinesin-dependent nuclear positioning is required for skeletal muscle function. Nature 484: 120–124.

5. FolkerES, SchulmanVK, BayliesMK (2012) Muscle length and myonuclear position are independently regulated by distinct Dynein pathways. Development 139: 3827–3837.

6. Elhanany-TamirH, YuYV, ShnayderM, JainA, WelteM, et al. (2012) Organelle positioning in muscles requires cooperation between two KASH proteins and microtubules. J Cell Biol 198: 833–846.

7. FolkerES, SchulmanVK, BayliesMK (2014) Translocating myonuclei have distinct leading and lagging edges that require kinesin and dynein. Development 141: 355–366.

8. GottaM, DongY, PetersonYK, LanierSM, AhringerJ (2003) Asymmetrically distributed C. elegans homologs of AGS3/PINS control spindle position in the early embryo. Curr Biol 13: 1029–1037.

9. HuangSH, DuanS, SunT, WangJ, ZhaoL, et al. (2011) JIP3 mediates TrkB axonal anterograde transport and enhances BDNF signaling by directly bridging TrkB with kinesin-1. J Neurosci 31: 10602–10614.

10. SetouM, SeogDH, TanakaY, KanaiY, TakeiY, et al. (2002) Glutamate-receptor-interacting protein GRIP1 directly steers kinesin to dendrites. Nature 417: 83–87.

11. SheemanB, CarvalhoP, SagotI, GeiserJ, KhoD, et al. (2003) Determinants of S. cerevisiae dynein localization and activation: implications for the mechanism of spindle positioning. Curr Biol 13: 364–372.

12. AbeN, Almenar-QueraltA, LilloC, ShenZ, LozachJ, et al. (2009) Sunday driver interacts with two distinct classes of axonal organelles. J Biol Chem 284: 34628–34639.

13. VerheyKJ, MeyerD, DeehanR, BlenisJ, SchnappBJ, et al. (2001) Cargo of kinesin identified as JIP scaffolding proteins and associated signaling molecules. J Cell Biol 152: 959–970.

14. ArimotoM, KoushikaSP, ChoudharyBC, LiC, MatsumotoK, et al. (2011) The Caenorhabditis elegans JIP3 protein UNC-16 functions as an adaptor to link kinesin-1 with cytoplasmic dynein. J Neurosci 31: 2216–2224.

15. DrerupCM, NechiporukAV (2013) JNK-interacting protein 3 mediates the retrograde transport of activated c-Jun N-terminal kinase and lysosomes. PLoS Genet 9: e1003303.

16. KamalA, StokinGB, YangZ, XiaCH, GoldsteinLS (2000) Axonal transport of amyloid precursor protein is mediated by direct binding to the kinesin light chain subunit of kinesin-I. Neuron 28: 449–459.

17. MatsudaS, MatsudaY, D'AdamioL (2003) Amyloid beta protein precursor (AbetaPP), but not AbetaPP-like protein 2, is bridged to the kinesin light chain by the scaffold protein JNK-interacting protein 1. J Biol Chem 278: 38601–38606.

18. McKenneyRJ, WeilSJ, SchererJ, ValleeRB (2011) Mutually exclusive cytoplasmic dynein regulation by NudE-Lis1 and dynactin. J Biol Chem 286: 39615–39622.

19. Rosa-FerreiraC, MunroS (2011) Arl8 and SKIP act together to link lysosomes to kinesin-1. Dev Cell 21: 1171–1178.

20. StockingerW, BrandesC, FaschingD, HermannM, GotthardtM, et al. (2000) The reelin receptor ApoER2 recruits JNK-interacting proteins-1 and -2. J Biol Chem 275: 25625–25632.

21. MontagnacG, SibaritaJB, LouberyS, DavietL, RomaoM, et al. (2009) ARF6 Interacts with JIP4 to control a motor switch mechanism regulating endosome traffic in cytokinesis. Curr Biol 19: 184–195.

22. SakamotoR, ByrdDT, BrownHM, HisamotoN, MatsumotoK, et al. (2005) The Caenorhabditis elegans UNC-14 RUN domain protein binds to the kinesin-1 and UNC-16 complex and regulates synaptic vesicle localization. Mol Biol Cell 16: 483–496.

23. VerheyKJ, LizotteDL, AbramsonT, BarenboimL, SchnappBJ, et al. (1998) Light chain-dependent regulation of Kinesin's interaction with microtubules. J Cell Biol 143: 1053–1066.

24. HsuCC, MoncaleanoJD, WagnerOI (2011) Sub-cellular distribution of UNC-104(KIF1A) upon binding to adaptors as UNC-16(JIP3), DNC-1(DCTN1/Glued) and SYD-2(Liprin-alpha) in C. elegans neurons. Neuroscience 176: 39–52.

25. GillSR, SchroerTA, SzilakI, SteuerER, SheetzMP, et al. (1991) Dynactin, a conserved, ubiquitously expressed component of an activator of vesicle motility mediated by cytoplasmic dynein. J Cell Biol 115: 1639–1650.

26. Waterman-StorerCM, KarkiSB, KuznetsovSA, TabbJS, WeissDG, et al. (1997) The interaction between cytoplasmic dynein and dynactin is required for fast axonal transport. Proc Natl Acad Sci U S A 94: 12180–12185.

27. TanoueM, YamagaM, IdeJ, TakagiK (1996) Acute stretching of peripheral nerves inhibits retrograde axonal transport. J Hand Surg Br 21: 358–363.

28. MiaoT, WuD, WheelerA, WangP, ZhangY, et al. (2011) Two cytokine signaling molecules co-operate to promote axonal transport and growth. Exp Neurol 228: 165–172.

29. NikitinaLS, DorofeevaNA, KirillovaOD, KorotkovAA, GlazovaM, et al. (2014) Role of the ERK signaling pathway in regulating vasopressin secretion in dehydrated rats. Biotech Histochem 89: 199–208.

30. HoriuchiD, CollinsCA, BhatP, BarkusRV, DiantonioA, et al. (2007) Control of a kinesin-cargo linkage mechanism by JNK pathway kinases. Curr Biol 17: 1313–1317.

31. CanoE, MahadevanLC (1995) Parallel signal processing among mammalian MAPKs. Trends Biochem Sci 20: 117–122.

32. GalloKA, JohnsonGL (2002) Mixed-lineage kinase control of JNK and p38 MAPK pathways. Nat Rev Mol Cell Biol 3: 663–672.

33. HerskowitzI (1995) MAP kinase pathways in yeast: for mating and more. Cell 80: 187–197.

34. Rios-BarreraLD, Riesgo-EscovarJR (2013) Regulating cell morphogenesis: the Drosophila Jun N-terminal kinase pathway. Genesis 51: 147–162.

35. RodriguezMC, PetersenM, MundyJ (2010) Mitogen-activated protein kinase signaling in plants. Annu Rev Plant Biol 61: 621–649.

36. WaskiewiczAJ, CooperJA (1995) Mitogen and stress response pathways: MAP kinase cascades and phosphatase regulation in mammals and yeast. Curr Opin Cell Biol 7: 798–805.

37. GomezAR, Lopez-VareaA, MolnarC, de la Calle-MustienesE, Ruiz-GomezM, et al. (2005) Conserved cross-interactions in Drosophila and Xenopus between Ras/MAPK signaling and the dual-specificity phosphatase MKP3. Dev Dyn 232: 695–708.

38. FuMM, HolzbaurEL (2013) JIP1 regulates the directionality of APP axonal transport by coordinating kinesin and dynein motors. J Cell Biol 202: 495–508.

39. CavalliV, KujalaP, KlumpermanJ, GoldsteinLS (2005) Sunday Driver links axonal transport to damage signaling. J Cell Biol 168: 775–787.

40. SunF, ZhuC, DixitR, CavalliV (2011) Sunday Driver/JIP3 binds kinesin heavy chain directly and enhances its motility. EMBO J 30: 3416–3429.

41. SunT, YuN, ZhaiLK, LiN, ZhangC, et al. (2013) c-Jun NH2-terminal kinase (JNK)-interacting protein-3 (JIP3) regulates neuronal axon elongation in a kinesin- and JNK-dependent manner. J Biol Chem 288: 14531–14543.

42. YasudaJ, WhitmarshAJ, CavanaghJ, SharmaM, DavisRJ (1999) The JIP group of mitogen-activated protein kinase scaffold proteins. Mol Cell Biol 19: 7245–7254.

43. KelkarN, StandenCL, DavisRJ (2005) Role of the JIP4 scaffold protein in the regulation of mitogen-activated protein kinase signaling pathways. Mol Cell Biol 25: 2733–2743.

44. IsabetT, MontagnacG, RegazzoniK, RaynalB, El KhadaliF, et al. (2009) The structural basis of Arf effector specificity: the crystal structure of ARF6 in a complex with JIP4. EMBO J 28: 2835–2845.

45. BowmanAB, KamalA, RitchingsBW, PhilpAV, McGrailM, et al. (2000) Kinesin-dependent axonal transport is mediated by the sunday driver (SYD) protein. Cell 103: 583–594.

46. BrandAH, PerrimonN (1993) Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 118: 401–415.

47. KelkarN, GuptaS, DickensM, DavisRJ (2000) Interaction of a mitogen-activated protein kinase signaling module with the neuronal protein JIP3. Mol Cell Biol 20: 1030–1043.

48. ByrdDT, KawasakiM, WalcoffM, HisamotoN, MatsumotoK, et al. (2001) UNC-16, a JNK-signaling scaffold protein, regulates vesicle transport in C. elegans. Neuron 32: 787–800.

49. SlussHK, HanZ, BarrettT, GoberdhanDC, WilsonC, et al. (1996) A JNK signal transduction pathway that mediates morphogenesis and an immune response in Drosophila. Genes Dev 10: 2745–2758.

50. WeberU, ParicioN, MlodzikM (2000) Jun mediates Frizzled-induced R3/R4 cell fate distinction and planar polarity determination in the Drosophila eye. Development 127: 3619–3629.

51. LouisM, PiccinottiS, VosshallLB (2008) High-resolution measurement of odor-driven behavior in Drosophila larvae. J Vis Exp.

52. HurdDD, SaxtonWM (1996) Kinesin mutations cause motor neuron disease phenotypes by disrupting fast axonal transport in Drosophila. Genetics 144: 1075–1085.

53. GhoM, McDonaldK, GanetzkyB, SaxtonWM (1992) Effects of kinesin mutations on neuronal functions. Science 258: 313–316.

54. ItoM, YoshiokaK, AkechiM, YamashitaS, TakamatsuN, et al. (1999) JSAP1, a novel jun N-terminal protein kinase (JNK)-binding protein that functions as a Scaffold factor in the JNK signaling pathway. Mol Cell Biol 19: 7539–7548.

55. EdwardsSL, YuSC, HooverCM, PhillipsBC, RichmondJE, et al. (2013) An organelle gatekeeper function for Caenorhabditis elegans UNC-16 (JIP3) at the axon initial segment. Genetics 194: 143–161.

56. LigonLA, TokitoM, FinklesteinJM, GrossmanFE, HolzbaurEL (2004) A direct interaction between cytoplasmic dynein and kinesin I may coordinate motor activity. J Biol Chem 279: 19201–19208.

57. HammondJW, GriffinK, JihGT, StuckeyJ, VerheyKJ (2008) Co-operative versus independent transport of different cargoes by Kinesin-1. Traffic 9: 725–741.

58. BlasiusTL, CaiD, JihGT, ToretCP, VerheyKJ (2007) Two binding partners cooperate to activate the molecular motor Kinesin-1. J Cell Biol 176: 11–17.

59. HaHY, ChoIH, LeeKW, LeeKW, SongJY, et al. (2005) The axon guidance defect of the telencephalic commissures of the JSAP1-deficient brain was partially rescued by the transgenic expression of JIP1. Dev Biol 277: 184–199.

60. RichardsonBE, BeckettK, NowakSJ, BayliesMK (2007) SCAR/WAVE and Arp2/3 are crucial for cytoskeletal remodeling at the site of myoblast fusion. Development 134: 4357–4367.

61. BrendzaKM, RoseDJ, GilbertSP, SaxtonWM (1999) Lethal kinesin mutations reveal amino acids important for ATPase activation and structural coupling. J Biol Chem 274: 31506–31514.

62. GepnerJ, LiM, LudmannS, KortasC, BoylanK, et al. (1996) Cytoplasmic dynein function is essential in Drosophila melanogaster. Genetics 142: 865–878.

63. GindhartJGJr, DesaiCJ, BeushausenS, ZinnK, GoldsteinLS (1998) Kinesin light chains are essential for axonal transport in Drosophila. J Cell Biol 141: 443–454.

64. CaggeseC, MoschettiR, RagoneG, BarsantiP, CaizziR (2001) dtctex-1, the Drosophila melanogaster homolog of a putative murine t-complex distorter encoding a dynein light chain, is required for production of functional sperm. Mol Genet Genomics 265: 436–444.

65. LeiY, WarriorR (2000) The Drosophila Lissencephaly1 (DLis1) gene is required for nuclear migration. Dev Biol 226: 57–72.

66. LiuZ, XieT, StewardR (1999) Lis1, the Drosophila homolog of a human lissencephaly disease gene, is required for germline cell division and oocyte differentiation. Development 126: 4477–4488.

67. ParmentierML, WoodsD, GreigS, PhanPG, RadovicA, et al. (2000) Rapsynoid/partner of inscuteable controls asymmetric division of larval neuroblasts in Drosophila. J Neurosci 20: RC84.

68. BayliesMK, BateM (1996) twist: a myogenic switch in Drosophila. Science 272: 1481–1484.

69. HalfonMS, CarmenaA, GisselbrechtS, SackersonCM, JimenezF, et al. (2000) Ras pathway specificity is determined by the integration of multiple signal-activated and tissue-restricted transcription factors. Cell 103: 63–74.

70. HalfonMS, GisselbrechtS, LuJ, EstradaB, KeshishianH, et al. (2002) New fluorescent protein reporters for use with the Drosophila Gal4 expression system and for vital detection of balancer chromosomes. Genesis 34: 135–138.

71. BrentJR, WernerKM, McCabeBD (2009) Drosophila larval NMJ dissection. J Vis Exp.

72. SchulmanVK, FolkerES, BayliesMK (2013) A method for reversible drug delivery to internal tissues of Drosophila embryos. Fly (Austin) 7: 193–203.

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2014 Číslo 12
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Eozinofilní granulomatóza s polyangiitidou
nový kurz
Autori: doc. MUDr. Martina Doubková, Ph.D.

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#