Transferencia de ARNs y ribosomas desde las glias a los axones

Contenido principal del artículo

José Roberto Sotelo

Resumen

Ha sido discutido durante muchas décadas si los axones contienen ARNs y ribosomas. En los últimos años se ha aceptado que ambos provienen del soma neuronal. Sin embargo, se ha abierto una nueva frontera de trabajo considerando un posible origen alternativo adicional de esos elementos: la glía adyacente al axón. En esta revisión nos dedicamos a enumerar las distintas pruebas que se han acumulado sobre la transferencia glía-axon de ARNs y ribosomas. Describimos estos procesos en axones de invertebrados y de vertebrados. Discutiremos sobre las interesantes implicancias que tiene el intercambio de ARNm (ARN mensajeros), los micros ARN (pequeños ARN o ARNmi, reguladores) y los ribosomas desde la glía al axón, respecto a la integración funcional entre las glias y los axones.Aunque es necesario todavía un mayor apoyo experimental para fundamentar este concepto, que se encuentra en evolución creciente y reciente, el mismo impacta fuertemente sobre nuestro entendimientode la biología molecular y celular de los axones tanto desde el punto de vista funcional como patológico. Posiblemente la fisiopatología de muchas enfermedades de los axones humanos, debe ser revisada exhaustivamente en relación a la posible participación de la transferencia de ribosomas y ARNs desde la glía al axón así como el efecto regulador de la glía sobre la síntesis proteica axonal.Estos nuevos elementos podrían aumentar las posibilidades de introducir intervenciones terapéuticas controladas durante la neurodegeneración o la injuria axonal.

Detalles del artículo

Cómo citar
Sotelo, J. R. (2016). Transferencia de ARNs y ribosomas desde las glias a los axones. Anales De La Facultad De Medicina, Universidad De La República, Uruguay, 3(1), 9-24. Recuperado a partir de https://anfamed.edu.uy/index.php/rev/article/view/189
Sección
Artículos de revisión
Biografía del autor/a

José Roberto Sotelo, Instituto de Investigaciones Biológicas Clemente Estable

Departamento de Proteínas y Ácidos NucleicosInstituto de Investigaciones Biológicas Clemente Estable

Citas


  1. Weiss P, Hiscoe HB. Experiments on the mechanism of nerve growth. J Exp Zool. 1948;107:315-95.

  2. Brady ST, Lasek RJ, Allen RD. Video microscopy of fast axonal transport in extruded axoplasm: a new model for study of molecular mechanisms. Cell Motil. 1985;5(2):81-101.

  3. Lasek RJ. Protein transport in neurons. Int Rev Neurobiol. 1970;13:289-324.

  4. Aschrafi A, Schwechter AD, Mameza MG, Natera-Naranjo O, Gioio AE, Kaplan BB. MicroRNA-338 regulates local cytochrome c oxidase IV mRNA levels and oxidative phosphorylation in the axons of sympathetic neurons. J Neurosci. 2008;28(47):12581–90. http://dx.doi.org/10.1523/JNEUROSCI.3338-08.2008

  5. Bassell GJ, Zhang H, Byrd AL, Femino AM, Singer RH, Taneja KL, et al. Sorting of beta-actin mRNA and protein to neurites and growth cones in culture. J Neurosci. 1998;18:251–65.

  6. Benech C, Sotelo JR Jr, Menendez J, Correa-Luna R. Autoradiographic study of RNA and protein synthesis in sectioned peripheral nerves. Exp Neurol. 1982; 76:72–82. http://dx.doi.org/10.1016/0014-4886(82)90102-9

  7. Calliari A, Farías J, Puppo A, Canclini L, Mercer J A, Munroe D, et al. Myosin Va associates with mRNA in ribonucleoprotein particles present in myelinated peripheral axons and in the central nervous system Dev Neurobiol. 2014 Mar;74(3):382-96. http://dx.doi.org/10.1002/dneu.22155

  8. Edstrom JE, Eichner D, Edstrom A. The ribonucleic acid of axons and myelin sheaths from Mauthner neurons. Biochim Biophys Acta. 1962;61:178–84.

  9. Eng H, Lund K, Campenot RB. Synthesis of beta-tubulin, actin, and other proteins in axons of sympathetic neurons in compartmented cultures. J Neurosci. 1999 Jan;19(1):1–9.

  10. Gumy LF, Yeo GS, Tung YC, Zivraj KH, Willis D, Coppola G, et al. Transcriptome analysis of embryonic and adult sensory axons reveals changes in mRNA repertoire localization. RNA. 2011;17(1):85–98. http://dx.doi.org/10.1261/rna.2386111

  11. Kaplan BB, Gioio AE, Hillefors M, Aschrafi A. Axonal protein synthesis and the regulation of local mitochondrial function. Results Probl Cell Differ. 2009;48:225–42. http://dx.doi.org/10.1007/400_2009_1

  12. Koenig E. Synthetic mechanisms in the axon. IV. In vitro incorporation of [3H]precursors into axonal protein and RNA. J Neurochem. 1967;14(4):437–46. http://dx.doi.org/10.1111/j.1471-4159.1967.tb09542.x

  13. Koenig E. Evaluation of local synthesis of axonal proteins in the goldfish Mauthner cell axon and axons of dorsal and ventral roots of the rat in vitro. Mol Cell Neurosci. 1991;2(5):384–94. http://dx.doi.org/10.1016/1044-7431(91)90025-J

  14. Koenig E, Martin R. Cortical plaque-like structures identify ribosome-containing domains in the Mauthner cell axon. J Neurosci. 1996;16(4):1400–11.

  15. Koenig E, Martin R, Titmus M, Sotelo-Silveira JR. Cryptic peripheral ribosomal domains distributed intermittently along mammalian myelinated axons. J Neurosci. 2000;20(22):8390–400.

  16. Kun A, Otero L, Sotelo-Silveira JR, Sotelo JR. Ribosomal distributions in axons of mammalian myelinated fibers. J Neurosci Res. 2007;85(10):2087–98. http://dx.doi.org/10.1002/jnr.21340

  17. Natera-Naranjo O, Aschrafi A, Gioio AE, Kaplan BB. Identification and quantitative analyses of microRNAs located in the distal axons of sympathetic neurons. RNA. 2010;16(8):1516–29. http://dx.doi.org/10.1261/rna.1833310

  18. Sotelo JR, Benech CR, Kun A. Local radiolabeling of the 68 kDa neurofilament protein in rat sciatic nerves. Neurosci Lett. 1992;144(1-2):174–6.

  19. Sotelo-Silveira JR, Calliari A, Kun A, Benech JC, Sanguinetti C, Chalar, C. Sotelo JR. Neurofilament mRNAs are present and translated in the normal and severed sciatic nerve. J Neurosci Res. 2000;62(1):65–74. http://dx.doi.org/10.1002/1097-4547(20001001)62:1<65::AID-JNR7>3.0.CO;2-Z

  20. Sotelo-Silveira JR, Calliari A, Cardenas M, Koenig E, Sotelo JR. Myosin Va and kinesin II motor proteins are concentrated in ribosomal domains (periaxoplasmic ribosomal plaques) of myelinated axons. J Neurobiol. 2004;60(2):187–96.

  21. Tasaki I, Hagiwara S. Demonstration of two stable potential states in the squid giant axon under tetraethylammonium chloride. J Gen Physiol. 1957;40(6):859-85.

  22. Willis D, Li KW, Zheng JQ, Chang JH, Smit AB, Kelly T, et al. Differential transport and local translation of cytoskeletal, injury-response, and neurodegeneration protein mRNAs in axons. J Neurosci. 2005;25(4):778–91. http://dx.doi.org/10.1523/JNEUROSCI.4235-04.2005

  23. Willis DE, van Niekerk EA, Sasaki Y, Mesngon M, Merianda TT, Williams GG, et al. Extracellular stimuli specifically regulate localized levels of individual neuronal mRNAs. J Cell Biol. 2007;178(6):965–80. http://dx.doi.org/10.1083/jcb.200703209

  24. Willis DE, Xu M, Donnelly CJ, Tep C, Kendall M, Erenstheyn M, et al. Axonal Localization of transgene mRNA in mature PNS and CNS neurons. J Neurosci. 2011;31(41):14481–7. http://dx.doi.org/10.1523/JNEUROSCI.2950-11.2011

  25. Zhang HL, Eom T, Oleynikov Y, Shenoy SM, Liebelt DA, Dictenberg JB, et al. Neurotrophin-induced transport of a beta-actin mRNP complex increases beta-actin levels and stimulates growth cone motility. Neuron. 2001;31(2):261–75. http://dx.doi.org/10.1016/S0896-6273(01)00357-9

  26. Zhang HL, Singer RH, Bassell GJ. Neurotrophin regulation of beta-actin mRNA and protein localization within growth cones. J Cell Biol. 1999;147(1):59–70. http://dx.doi.org/10.1083/jcb.147.1.59

  27. Zivraj KH, Tung YC, Piper M, Gumy L, Fawcett JW, Yeo GS, et al. Subcellular profiling reveals distinct and developmentally regulated repertoire of growth cone mRNAs. J Neurosci. 2010;30(46):15464–78. http://dx.doi.org/10.1523/JNEUROSCI.1800-10.2010

  28. Alvarez J, Giuditta A, Koenig E. Protein synthesis in axons and terminals: significance for maintenance, plasticity and regulation of phenotype. With a critique of slow transport theory. Prog Neurobiol. 2000;62(1):1–62. http://dx.doi.org/10.1016/S0301-0082(99)00062-3

  29. Eyman M, Cefaliello C, Ferrara E, De Stefano R, Lavina ZS, Crispino M, et al. Local synthesis of axonal and presynaptic RNA in squid model systems. Eur J Neurosci. 2007;25(2):341–50. http://dx.doi.org/10.1111/j.1460-9568.2007.05304.x

  30. Gainer H, Tasaki I, Lasek RJ. Evidence for the glia-neuron protein transfer hypothesis from intracellular perfusion studies of squid giant axons. J Cell Biol. 1977;74(2):524–30.

  31. Giuditta A, Kaplan BB, van Minnen J, Alvarez J, Koenig E. Axonal and presynaptic protein synthesis: new insights into the biology of the neuron. Trends Neurosci. 2002;25(8):400–4. http://dx.doi.org/10.1016/S0166-2236(02)02188-4

  32. Koenig E, Giuditta A. Protein-synthesizing machinery in the axon compartment. Neuroscience. 1999;89(1):5–15. http://dx.doi.org/10.1016/S0306-4522(98)00282-6

  33. Piper M, Holt C. RNA translation in axons. Annu Rev Cell Dev Biol. 2004;20:50523. http://dx.doi.org/10.1146/annurev.cellbio.20.010403.111746

  34. Sotelo-Silveira JR, Calliari A, Kun A, Koenig E, Sotelo JR. RNA trafficking in axons. Traffic. 2006;7(5):508–15. http://dx.doi.org/10.1111/j.1600-0854.2006.00405.x

  35. Taylor AM, Berchtold NC, Perreau VM, Tu CH, Li Jeon N, Cotman CW. Axonal mRNA in uninjured and regenerating cortical mammalian axons. J Neurosci. 2009;29(15):4697–707.

  36. Taylor AM, Wu J, Tai HC, Schuman EM. Axonal translation of beta-catenin regulates synaptic vesicle dynamics. J Neurosci. 2013;33(13):5584–9. http://dx.doi.org/10.1523/JNEUROSCI.2944-12.2013.

  37. Bassell GJ, Oleynikov Y, Singer RH. The travels of mRNAs through all cells large and small. FASEB J. 1999;13:447–54.

  38. Bassell GJ, Singer RH. Neuronal RNA localization and the cytoskeleton. Results Probl Cell Differ. 2001;34:41-56.

  39. Ben-Yaakov K, Dagan SY, Segal-Ruder Y, Shalem O, Vuppalanchi D, Willis DE, et al. Axonal transcription factors signal retrogradely in lesioned peripheral nerve. EMBO J. 2012;31(6):1350–63. http://dx.doi.org/10.1038/emboj.2011.494

  40. Sotelo-Silveira J, Crispino M, Puppo A, Sotelo JR, Koenig E. Myelinated axons contain beta-actin mRNA and ZBP-1 in periaxoplasmic ribosomal plaques and depend on cyclic AMP and F-actin integrity for in vitro translation. J Neurochem. 2008;104:545–57. http://dx.doi.org/10.1111/j.1471-4159.2007.04999.x

  41. Long RM, Gu W, Lorimer E, Singer RH, Chartrand P. She2p is a novel RNA-binding protein that recruits the Myo4p-She3p complex to ASH1 mRNA. EMBO J. 2000;19(23):6592–601. http://dx.doi.org/10.1093/emboj/19.23.6592

  42. Long RM, Singer RH, Meng X, Gonzalez I, Nasmyth K, Jansen RP. Mating type switching in yeast controlled by asymmetric localization of ASH1 mRNA. Science. 1997;277(5324):383–7.

  43. Vogelaar CF, Gervasi NM, Gumy LF, Story DJ, Raha-Chowdhury R, Leung KM, et al. Axonal mRNAs: Characterisation and role in the growth and regeneration of dorsal root ganglion axons and growth cones. Mol Cell Neurosci. 2009;42(2):102–15. http://dx.doi.org/10.1016/j.mcn.2009.06.002

  44. Rapallino MV, Cupello A, Giuditta A. Axoplasmic RNA species synthesized in the isolated squid giant axon. Neurochem Res. 1988;13(7):625–31.

  45. Sotelo JR, Canclini L, Kun A, Sotelo-Silveira JR, Xu L, Wallrabe H, et al. Myosin-Va-dependent cell-to-cell transfer of RNA from Schwann cells to axons. PLoS One [Internet]. 2013 [consultado 2016 jul 22],8(4):e61905. Disponible en: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0061905 http://dx.doi.org/10.1371/journal.pone.0061905. Print 2013

  46. Zelena J. Ribosome-like particles in myelinated axons of the rat. Brain Res. 1970;24(2):359–63. http://dx.doi.org/10.1016/0006-8993(70)90120-4

  47. Zelena J. Ribosomes in myelinated axons of dorsal root ganglia. Z Zellforsch Mikrosk Anat. 1972;124(2):217–29.

  48. Zelena J. Ribosomes in the axoplasm of myelinated nerve fibres. Folia Morphol (Praha). 1972. 20(1):91–3.

  49. Li YC, Cheng CX, Li YN, Shimada O, Atsumi S. Beyond the initial axon segment of the spinal motor axon: fasciculated microtubules and polyribosomal clusters. J Anat. 2005;206(6):535–42. http://dx.doi.org/10.1111/j.1469-7580.2005.00418.x

  50. Li YC, Li YN, Cheng CX, Sakamoto H, Kawate T, Shimada O, et al. Subsurface cisterna-lined axonal invaginations and double-walled vesicles at the axonal-myelin sheath interface. Neurosci Res. 2005;53(3):298–303. http://dx.doi.org/10.1016/j.neures.2005.07.006

  51. Court FA, Hendriks WT, MacGillavry HD, Alvarez J, van Minnen J. Schwann cell to axon transfer of ribosomes: toward a novel understanding of the role of glia in the nervous system. J Neurosci. 2008;28(43):11024–9. http://dx.doi.org/10.1523/JNEUROSCI.2429-08.2008

  52. Court FA, Midha R, Cisterna BA, Grochmal J, Shakhbazau A, Hendriks WT, et al. Morphological evidence for a transport of ribosomes from Schwann cells to regenerating axons. Glia. 2011;59(10):1529–39. http://dx.doi.org/10.1002/glia.21196

  53. Singer M, Green MR. Autoradiographic studies of uridine incorporation in peripheral nerve of the newt, Triturus. J Morphol. 1968;124(3):321–44.

  54. Rustom A, Saffrich R, Markovic I, Walther P, Gerdes HH. Nanotubular highways for intercellular organelle transport. Science. 2004;303(5660):1007–10. http://dx.doi.org/10.1126/science.1093133

  55. Palacios IM. RNA processing: splicing and the cytoplasmic localisation of mRNA. Curr Biol. 2002;12(2):R50–R52. http://dx.doi.org/10.1016/S0960-9822(01)00671-6

  56. Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007;9(6):654–9. http://dx.doi.org/10.1038/ncb1596

  57. Boissy RE. Melanosome transfer to and translocation in the keratinocyte. Exp Dermatol. 2003;12 Suppl 2:5–12. http://dx.doi.org/10.1034/j.1600-0625.12.s2.1.x

  58. Spees JL, Olson SD, Whitney MJ, Prockop DJ. Mitochondrial transfer between cells can rescue aerobic respiration. Proc Natl Acad Sci USA. 2006;103(5):1283–8. http://dx.doi.org/10.1073/pnas.0510511103

  59. Lasek RJ, Gainer H, Barker JL. Cell-to-cell transfer of glial proteins to the squid giant axon. The glia-neuron protein transfer hypothesis. J Cell Biol. 1977;74(2):501–23.

  60. Tytell M, Lasek RJ, Gainer H. Axonal maintenance, glia, exosomes, and heat shock proteins. F1000Res [Internet]. 2016 [consultado 2016 jul 22];5(F1000 Faculty Rev):205. Disponible en: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4765724/ http://dx.doi.org/10.12688/f1000research.7247.1

  61. Lasek RJ, Gainer H, Przybylski RJ. Transfer of newly synthesized proteins from Schwann cells to the squid giant axon. Proc Natl Acad Sci. USA. 1974;71(4):118892.

  62. Giuditta A, Chun JT, Eyman M, Cefaliello C, Bruno AP, Crispino M. Local gene expression in axons and nerve endings: the glia-neuron unit. Physiol Rev. 2008;88(2):515–55. http://dx.doi.org/10.1152/physrev.00051.2006

  63. Giuditta A, Kaplan BB, van Minnen J, Alvarez J, Koenig E. Axonal and presynaptic protein synthesis: new insights into the biology of the neuron. Trends Neurosci. 2002;25(8):400–4. http://dx.doi.org/10.1016/S0166-2236(02)02188-4

  64. Kaplan BB, Gioio AE, Capano CP, Crispino M, Giuditta A. beta-Actin and beta-Tubulin are components of a heterogeneous mRNA population present in the squid giant axon. Mol Cell Neurosci. 1992;3(2):133–44. http://dx.doi.org/10.1016/1044-7431(92)90017-V

  65. Crispino M, Kaplan BB, Martin R, Alvarez J, Chun JT, Benech JC, et al. Active polysomes are present in the large presynaptic endings of the synaptosomal fraction from squid brain. J Neurosci. 1997;17(20):7694–702.

  66. Gambetti P, Autilio-Gambetti L, Shafer B, Pfaff LD. Quantitative autoradiographic study of labeled RNA in rabbit optic nerve after intraocular injection of [3H]uridine. J Cell Biol. 1973;59:677–84.

  67. Lunn ER, Perry VH, Brown MC, Rosen H, Gordon S. Absence of Wallerian degeneration does not Hinder regeneration in peripheral nerve. Eur J Neurosci. 1989;1(1):27–33.

  68. Mack TG, Reiner M, Beirowski B, Mi W, Emanuelli M, Wagner D, Thomson D, et al. Wallerian degeneration of injured axons and synapses is delayed by a Ube4b/Nmnat chimeric gene. Nat Neurosci. 2001;4:1199–206. http://dx.doi.org/10.1111/j.1460-9568.1989.tb00771.x

  69. Araki T, Sasaki Y, Milbrandt J. Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal degeneration. Science. 2004;305(5686):1010–3. http://dx.doi.org/10.1126/science.1098014

  70. Coleman MP, Conforti L, Buckmaster EA, Tarlton A, Ewing RM, Brown MC, et al. An 85-kb tandem triplication in the slow Wallerian degeneration (Wlds) mouse. Proc Natl Acad Sci USA. 1998;95(17):9985–90.

  71. Conforti L, Fang G, Beirowski B, Wang MS, Sorci L, Asress S, et al. NAD(+) and axon degeneration revisited: Nmnat1 cannot substitute for Wld(S) to delay Wallerian degeneration. Cell Death Differ. 2007;14(1):116–27. http://dx.doi.org/10.1038/sj.cdd.4401944

  72. Shakhbazau A, Schenk GJ, Hay C, Kawasoe J, Klaver R, Yong VW, et al. Demyelination induces transport of ribosome-containing vesicles from glia to axons: evidence from animal models and MS patient brains. Mol Biol Rep. 2016;43(6):495-507. http://dx.doi.org/10.1007/s11033-016-3990-2

  73. Massardo L, Burgos P, Martinez ME, Perez R, Calvo M, Barros J, et al. Antiribosomal P protein antibodies in Chilean SLE patients: no association with renal disease. Lupus. 2002;11(6):379–83.

  74. Canclini L, Wallrabe H, Di Paolo P, Kun A, Calliari A, Sotelo-Silveira JR, et al. Association of Myosin Va and Schwann Cells-derived RNA in mammal myelinated axons, analyzed by immunocytochemistry and confocal FRET microscopy. Methods. 2014;66(2):153–61. http://dx.doi.org/10.1016/j.ymeth.2013.06.007

  75. Frühbeis C1, Fröhlich D, Kuo WP, Amphornrat J, Thilemann S, Saab AS, et al. Neurotransmitter-triggered transfer of exosomes mediates oligodendrocyte-neuron communication. PLoS Biol [Internet]. 2013 [consultado 2016 jul 22];11(7):e1001604. Disponible en: http://dx.doi.org/10.1371/journal.pbio.1001604

  76. Frühbeis C, Fröhlich D, Kuo WP, Krämer-Albers EM. Extracellular vesicles as mediators of neuron-glia communication. Front Cell Neurosci. 2013;7:182. http://dx.doi.org/10.3389/fncel.2013.00182.

  77. Basso M, Bonetto V. Extracellular vesicles and a novel form of communication in the brain. Front Neurosci. 2016;10:127. http://dx.doi.org/10.3389/fnins.2016.00127. eCollection 2016.