The Vesicle Protein SAM-4 Regulates the Processivity of Synaptic Vesicle Transport

English version České info

Most cellular components of neurons are synthesized in the cell body and must be transported great distances to form synapses at the ends of axons and dendrites. Neurons use a specialized axonal transport system consisting of microtubule cytoskeletal tracks and numerous molecular motors to shuttle specific cargo to specific destinations in the cell. Disruption of this transport system has severe consequences to human health. Disruption of specific neuronal motors are linked to hereditary neurodegenerative conditions including forms of Charcot Marie Tooth disease, several types of hereditary spastic paraplegia, and certain forms of amyotrophic lateral sclerosis motor neuron disease. Despite recent progress in defining the cargo of many of kinesin family motors in neurons, little is known about how the activity of these transport systems is regulated. Here, using a simple invertebrate model we identify and characterize a novel protein that regulates the efficacy of the KIF1A motor that mediates transport of synaptic vesicles. These studies define a new pathway regulating SV transport with potential links to human neurological disease.

Vyšlo v časopise: The Vesicle Protein SAM-4 Regulates the Processivity of Synaptic Vesicle Transport. PLoS Genet 10(10): e32767. doi:10.1371/journal.pgen.1004644
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004644

Souhrn

Zdroje

1. GoldsteinAY, WangX, SchwarzTL (2008) Axonal transport and the delivery of pre-synaptic components. Curr Opin Neurobiol 18 : 495–503.

2. HirokawaN, NiwaS, TanakaY (2010) Molecular motors in neurons: transport mechanisms and roles in brain function, development, and disease. Neuron 68 : 610–638.

3. EspositoG, FernandesAC, VerstrekenP (2011) Synaptic vesicle trafficking and Parkinson's disease. Dev Neurobiol 72 : 134–144.

4. SalinasS, BilslandLG, SchiavoG (2008) Molecular landmarks along the axonal route: axonal transport in health and disease. Curr Opin Cell Biol 20 : 445–453.

5. RiviereJB, RamalingamS, LavastreV, ShekarabiM, HolbertS, et al. (2011) KIF1A, an axonal transporter of synaptic vesicles, is mutated in hereditary sensory and autonomic neuropathy type 2. Am J Hum Genet 89 : 219–230.

6. KlebeS, LossosA, AzzedineH, MundwillerE, ShefferR, et al. (2012) KIF1A missense mutations in SPG30, an autosomal recessive spastic paraplegia: distinct phenotypes according to the nature of the mutations. Eur J Hum Genet 20 : 645–649.

7. SiddiquiSS (2002) Metazoan motor models: kinesin superfamily in C. elegans. Traffic 3 : 20–28.

8. MikiH, SetouM, KaneshiroK, HirokawaN (2001) All kinesin superfamily protein, KIF, genes in mouse and human. Proc Natl Acad Sci U S A 98 : 7004–7011.

9. HirokawaN, NodaY (2008) Intracellular transport and kinesin superfamily proteins, KIFs: structure, function, and dynamics. Physiol Rev 88 : 1089–1118.

10. 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.

11. GlaterEE, MegeathLJ, StowersRS, SchwarzTL (2006) Axonal transport of mitochondria requires milton to recruit kinesin heavy chain and is light chain independent. J Cell Biol 173 : 545–557.

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

13. HammondJW, BlasiusTL, SoppinaV, CaiD, VerheyKJ (2010) Autoinhibition of the kinesin-2 motor KIF17 via dual intramolecular mechanisms. J Cell Biol 189 : 1013–1025.

14. HammondJW, CaiD, BlasiusTL, LiZ, JiangY, et al. (2009) Mammalian Kinesin-3 motors are dimeric in vivo and move by processive motility upon release of autoinhibition. PLoS Biol 7: e72.

15. ImanishiM, EndresNF, GennerichA, ValeRD (2006) Autoinhibition regulates the motility of the C. elegans intraflagellar transport motor OSM-3. J Cell Biol 174 : 931–937.

16. KaanHY, HackneyDD, KozielskiF (2011) The structure of the kinesin-1 motor-tail complex reveals the mechanism of autoinhibition. Science 333 : 883–885.

17. FriedmanDS, ValeRD (1999) Single-molecule analysis of kinesin motility reveals regulation by the cargo-binding tail domain. Nat Cell Biol 1 : 293–297.

18. StockMF, GuerreroJ, CobbB, EggersCT, HuangTG, et al. (1999) Formation of the compact confomer of kinesin requires a COOH-terminal heavy chain domain and inhibits microtubule-stimulated ATPase activity. J Biol Chem 274 : 14617–14623.

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

20. ChoKI, YiH, DesaiR, HandAR, HaasAL, et al. (2009) RANBP2 is an allosteric activator of the conventional kinesin-1 motor protein, KIF5B, in a minimal cell-free system. EMBO Rep 10 : 480–486.

21. MorfiniG, SzebenyiG, ElluruR, RatnerN, BradyST (2002) Glycogen synthase kinase 3 phosphorylates kinesin light chains and negatively regulates kinesin-based motility. Embo J 21 : 281–293.

22. GuillaudL, WongR, HirokawaN (2008) Disruption of KIF17-Mint1 interaction by CaMKII-dependent phosphorylation: a molecular model of kinesin-cargo release. Nat Cell Biol 10 : 19–29.

23. LiuJS, SchubertCR, FuX, FourniolFJ, JaiswalJK, et al. (2012) Molecular basis for specific regulation of neuronal kinesin-3 motors by doublecortin family proteins. Mol Cell 47 : 707–721.

24. Serra-PagesC, KedershaNL, FazikasL, MedleyQ, DebantA, et al. (1995) The LAR transmembrane protein tyrosine phosphatase and a coiled-coil LAR-interacting protein co-localize at focal adhesions. EMBO J 14 : 2827–2838.

25. Serra-PagesC, MedleyQG, TangM, HartA, StreuliM (1998) Liprins, a family of LAR transmembrane protein-tyrosine phosphatase-interacting proteins. J Biol Chem 273 : 15611–15620.

26. KoJ, KimS, ValtschanoffJG, ShinH, LeeJR, et al. (2003) Interaction between liprin-alpha and GIT1 is required for AMPA receptor targeting. J Neurosci 23 : 1667–1677.

27. WyszynskiM, KimE, DunahAW, PassafaroM, ValtschanoffJG, et al. (2002) Interaction between GRIP and liprin-alpha/SYD2 is required for AMPA receptor targeting. Neuron 34 : 39–52.

28. DaiY, TaruH, DekenSL, GrillB, AckleyB, et al. (2006) SYD-2 Liprin-alpha organizes presynaptic active zone formation through ELKS. Nat Neurosci 9 : 1479–1487.

29. 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.

30. StigloherC, ZhanH, ZhenM, RichmondJ, BessereauJL (2011) The presynaptic dense projection of the Caenorhabditis elegans cholinergic neuromuscular junction localizes synaptic vesicles at the active zone through SYD-2/liprin and UNC-10/RIM-dependent interactions. J Neurosci 31 : 4388–4396.

31. SpanglerSA, HoogenraadCC (2007) Liprin-alpha proteins: scaffold molecules for synapse maturation. Biochem Soc Trans 35 : 1278–1282.

32. ShinH, WyszynskiM, HuhKH, ValtschanoffJG, LeeJR, et al. (2003) Association of the kinesin motor KIF1A with the multimodular protein liprin-alpha. J Biol Chem 278 : 11393–11401.

33. MillerKE, DeProtoJ, KaufmannN, PatelBN, DuckworthA, et al. (2005) Direct observation demonstrates that Liprin-alpha is required for trafficking of synaptic vesicles. Curr Biol 15 : 684–689.

34. WagnerOI, EspositoA, KohlerB, ChenCW, ShenCP, et al. (2009) Synaptic scaffolding protein SYD-2 clusters and activates kinesin-3 UNC-104 in C. elegans. Proc Natl Acad Sci U S A 106 : 19605–19610.

35. MontpetitA, BoilyG, SinnettD (2002) A detailed transcriptional map of the chromosome 12p12 tumour suppressor locus. Eur J Hum Genet 10 : 62–71.

36. ErnstromGG, ChalfieM (2002) Genetics of sensory mechanotransduction. Annu Rev Genet 36 : 411–453.

37. ChalfieM, SulstonJE, WhiteJG, SouthgateE, ThomsonJN, et al. (1985) The neural circuit for touch sensitivity in Caenorhabditis elegans. J Neurosci 5 : 956–964.

38. HamelinM, ScottIM, WayJC, CulottiJG (1992) The mec-7 beta-tubulin gene of Caenorhabditis elegans is expressed primarily in the touch receptor neurons. EMBO J 11 : 2885–2893.

39. NonetML (1999) Visualization of synaptic specializations in live C. elegans with synaptic vesicle protein-GFP fusions. J Neurosci Methods 89 : 33–40.

40. WhiteJG, SouthgateE, ThomsonJN, BrennerS (1986) The structure of the nervous system of the nematode Caenorhabditis elegans. Philos Trans R Soc Lond B Biol Sci 314 : 1–340.

41. KoushikaSP, SchaeferAM, VincentR, WillisJH, BowermanB, et al. (2004) Mutations in Caenorhabditis elegans cytoplasmic dynein components reveal specificity of neuronal retrograde cargo. J Neurosci 24 : 3907–3916.

42. Schaefer AM (2001) A Molecular Genetic Analysis of Synapse Formation in C. elegans [PhD]. St. Louis, MO: Washington University 129 p.

43. MahoneyTR, LiuQ, ItohT, LuoS, HadwigerG, et al. (2006) Regulation of synaptic transmission by RAB-3 and RAB-27 in Caenorhabditis elegans. Mol Biol Cell 17 : 2617–2625.

44. HallDH, HedgecockEM (1991) Kinesin-related gene unc-104 is required for axonal transport of synaptic vesicles in C. elegans. Cell 65 : 837–847.

45. Frokjaer-JensenC, DavisMW, HopkinsCE, NewmanBJ, ThummelJM, et al. (2008) Single-copy insertion of transgenes in Caenorhabditis elegans. Nat Genet 40 : 1375–1383.

46. Frokjaer-JensenC, DavisMW, AilionM, JorgensenEM (2012) Improved Mos1-mediated transgenesis in C. elegans. Nat Methods 9 : 117–118.

47. NonetML, GrundahlK, MeyerBJ, RandJB (1993) Synaptic function is impaired but not eliminated in C. elegans mutants lacking synaptotagmin. Cell 73 : 1291–1305.

48. JohnsonDR, BhatnagarRS, KnollLJ, GordonJI (1994) Genetic and biochemical studies of protein N-myristoylation. Annu Rev Biochem 63 : 869–914.

49. KlopfensteinDR, TomishigeM, StuurmanN, ValeRD (2002) Role of phosphatidylinositol(4,5)bisphosphate organization in membrane transport by the Unc104 kinesin motor. Cell 109 : 347–358.

50. KlopfensteinDR, ValeRD (2004) The lipid binding pleckstrin homology domain in UNC-104 kinesin is necessary for synaptic vesicle transport in Caenorhabditis elegans. Mol Biol Cell 15 : 3729–3739.

51. KumarJ, ChoudharyBC, MetpallyR, ZhengQ, NonetML, et al. (2010) The Caenorhabditis elegans Kinesin-3 motor UNC-104/KIF1A is degraded upon loss of specific binding to cargo. PLoS Genet 6: e1001200.

52. AveryL, HorvitzHR (1989) Pharyngeal pumping continues after laser killing of the pharyngeal nervous system of C. elegans. Neuron 3 : 473–485.

53. OuCY, PoonVY, MaederCI, WatanabeS, LehrmanEK, et al. (2010) Two cyclin-dependent kinase pathways are essential for polarized trafficking of presynaptic components. Cell 141 : 846–858.

54. KikkawaM, SablinEP, OkadaY, YajimaH, FletterickRJ, et al. (2001) Switch-based mechanism of kinesin motors. Nature 411 : 439–445.

55. SchwickartM, HavlisJ, HabermannB, BogdanovaA, CamassesA, et al. (2004) Swm1/Apc13 is an evolutionarily conserved subunit of the anaphase-promoting complex stabilizing the association of Cdc16 and Cdc27. Mol Cell Biol 24 : 3562–3576.

56. SonnichsenB, KoskiLB, WalshA, MarschallP, NeumannB, et al. (2005) Full-genome RNAi profiling of early embryogenesis in Caenorhabditis elegans. Nature 434 : 462–469.

57. GreenRA, KaoHL, AudhyaA, ArurS, MayersJR, et al. (2011) A high-resolution C. elegans essential gene network based on phenotypic profiling of a complex tissue. Cell 145 : 470–482.

58. UpdikeDL, StromeS (2009) A genomewide RNAi screen for genes that affect the stability, distribution and function of P granules in Caenorhabditis elegans. Genetics 183 : 1397–1419.

59. PuramSV, BonniA (2011) Novel functions for the anaphase-promoting complex in neurobiology. Semin Cell Dev Biol 22 : 586–594.

60. JuoP, KaplanJM (2004) The anaphase-promoting complex regulates the abundance of GLR-1 glutamate receptors in the ventral nerve cord of C. elegans. Curr Biol 14 : 2057–2062.

61. van RoesselP, ElliottDA, RobinsonIM, ProkopA, BrandAH (2004) Independent regulation of synaptic size and activity by the anaphase-promoting complex. Cell 119 : 707–718.

62. BrennerS (1974) The genetics of Caenorhabditis elegans. Genetics 77 : 71–94.

63. PraitisV, CaseyE, CollarD, AustinJ (2001) Creation of low-copy integrated transgenic lines in Caenorhabditis elegans. Genetics 157 : 1217–1226.

64. De StasioEA, DormanS (2001) Optimization of ENU mutagenesis of Caenorhabditis elegans. Mutat Res 495 : 81–88.

65. FisherCL, PeiGK (1997) Modification of a PCR-based site-directed mutagenesis method. Biotechniques 23 : 570–574, 570-571, 574.

66. RamotD, JohnsonBE, BerryTLJr, CarnellL, GoodmanMB (2008) The Parallel Worm Tracker: a platform for measuring average speed and drug-induced paralysis in nematodes. PLoS One 3: e2208.

67. HadwigerG, DourS, ArurS, FoxP, NonetML (2010) A monoclonal antibody toolkit for C. elegans. PLoS One 5: e10161.

68. NonetML, StauntonJ, KilgardMP, FergestadT, HartweigE, et al. (1997) C. elegans rab-3 mutant synapses exhibit impaired function and are partially depleted of vesicles. J Neurosci 17 : 8021–8073.

69. ChristopherFang-Yen, SaraWasserman, PialiSengupta, SamuelADT (2009) Agarose immobilization of C. elegans. The Worm Breeder's Gazette 18 : 32–32.