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Autophagosomes and multivesicular bodies in neuronal development and degeneration

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Translational Neuroscience

Abstract

A growing body of research deals with the relationship between the endosomal and autophagic/lysosomal pathways during developmental stages of the central nervous system. This includes their possible influence regarding the onset and progression of specific neurodegenerative disorders. In this review we focus our attention on major alterations affecting two organelles: autophagosomes and multivesicular bodies, both of which are located at the intersection point of their respective pathways.

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References

  1. Cooney J.R., Hurlburt J.L., Selig D.K., Harris K.M., Fiala J.C., Endosomal compartments serve multiple hippocampal dentritic spines from a widespread rather than a local store of recycling membrane, J. Neurosci. 2002, 22, 2215–2224

    PubMed  CAS  Google Scholar 

  2. Roizin L., Nishikawa K., Koizumi J., Keoseian S., The fine structure of the multivesicular body and their relationship to the ultracellular constituents of the central nervous system, J. Neuropathol. Exp. Neurol., 1967, 26, 223–249

    Article  PubMed  CAS  Google Scholar 

  3. Yamamoto T., On the thickness of the unit membrane, J. Cell Biol., 1963, 382, 217–226

    Google Scholar 

  4. Castel M. N., Woulfe J., Wang X., Laduron P. M., Beaudet A., Light and electron microscopic localization of retrogradely transported neurotensin in rat nigrostriatal dopaminergic neurons, Neuroscience, 1992, 50, 269–282

    Article  PubMed  CAS  Google Scholar 

  5. Delcroix J. D., Valletta J. S., Wu C., Hunt S. J., Kowal A. S., Mobley W.C., NGF signaling in sensory neurons: evidence that early endosomes carry NGF retrograde signals, Neuron, 2003, 39, 69–84

    Article  PubMed  CAS  Google Scholar 

  6. Kappeller K., Mayor D., An electron microscopic study of the early changes distal to a constriction in sympathetic nerves, Proc. R. Soc. Lond. B. Biol. Sci., 1969, 172, 53–63

    Article  Google Scholar 

  7. Christopher S. Von Bartheld, Amy L. Altick, Multivesicular bodies in neurons: Distribution, protein content, and trafficking function, Prog. Neurobiol., 2011, 93, 313–340

    Article  Google Scholar 

  8. Murphy R. F., Maturation models for endosome and lysosome biogenesis, Trends Cell Biol., 1991, 1, 77–82

    Article  PubMed  CAS  Google Scholar 

  9. van Deurs B., Holm P. K., Kayser L., Sandvig K., Hansen S. H., Multivesicular bodies in HEp-2 cells are maturing endosomes, Eur. J. Cell Biol., 1993, 61, 208–224

    PubMed  Google Scholar 

  10. Gruenberg J., Griffiths G., Howell K. E., Caracterization of the early endosome and putative endocytic carrier vesicles in vivo and with an assay of vesicle fusion in vitro, J. Cell Biol., 1989, 108, 1301–1316

    Article  PubMed  CAS  Google Scholar 

  11. Mullock, B. M., Bright N. A., Fearon C. W., Gray S. R., Luzio J. P., Fusion of lysosomes with late endosomes produces a hybrid organelle of intermediate density and is NSF dependent, J. Cell Biol., 1998, 140, 591–601

    Article  PubMed  CAS  Google Scholar 

  12. Vonderheit A., Helenius, A., Rab7 associates with early endosomes to mediate sorting and transport of Semliki forest virus to late endosomes, PLoS Biol., 2005, 3, e233

    Article  PubMed  Google Scholar 

  13. Dunn W.A.Jr., Studies on the mechanisms of autophagy: maturation of the autophagic vacuole, J. Cell Biol., 1990, 110, 1935–1945

    Article  PubMed  CAS  Google Scholar 

  14. Kilionsky D.J., Emr S.D., Autophagy as a regulated pathway of cellular degradation, Science, 2000, 290, 1717–1721

    Article  Google Scholar 

  15. Mizushima N., Levine B., Cuervo A.M., Klionsky D.J., Autophagy fights desease through cellular self-digestion, Nature, 2008, 451, 1069–1075

    Article  PubMed  CAS  Google Scholar 

  16. Yang Z., Klionsky D.J., Eaten alive: a history of macroautophagy, Nat. Cell Biol., 2010, 12, 814–822

    Article  PubMed  CAS  Google Scholar 

  17. Maiuri M.C., Zalckvar E., Kimchi A., Kroemer G., Selfeating and selfkilling: crosstalk between autophagy and apoptosis, Nat. Rev. Mol. Cell Biol., 2007, 8, 741–752

    Article  PubMed  CAS  Google Scholar 

  18. Xie Z., Klionsky D.J., Autophagosome formation: core machinery and adaptations, Nat. Cell Biol., 2007, 9, 1102–1109

    Article  PubMed  CAS  Google Scholar 

  19. He C., Klionsky D.J., Regulation mechanisms and signaling pathways of autophagy, Annu. Rev. Genet., 2009, 43, 67–93

    Article  PubMed  CAS  Google Scholar 

  20. Butowt R., von Bartheld C.S., Sorting of internalized neurotrophins into an endocytic transcytosis pathway via the Golgi system: ultrastructural analysis in retinal ganglion cells, J. Neurosci., 2001, 21, 8915–8930

    PubMed  CAS  Google Scholar 

  21. Chu-Wang I.W., Oppenheim R.W., Uptake, intra-axonal transport and fate of horseradish peroxidase in embryonic spinal neurons of the chick, J. Comp. Neurol., 1980, 193, 753–776

    Article  PubMed  CAS  Google Scholar 

  22. Rind H.B., Butowt R., von Bartheld C.S., Synaptic targeting of retrogradely transported trophic factors in motoneurons: comparison of glial cell line derived neurotrophic factor, brainderived neurotrophic factor, and cardiotrophin-1 with tetanus toxin, J. Neurosci., 2007, 25, 539–549

    Article  Google Scholar 

  23. Vitalis T., Laine J., Simon A., Roland A., Leterrier C., Lenkei Z., The type 1 cannabinoid receptor is highly expressed in embryonic cortical projection neurons and negatively regulates neurite growth in vitro, Eur. J. Neurosci., 2008, 28, 1705–1718

    Article  PubMed  Google Scholar 

  24. Alberts P., Galli T., The cell outgrowth secretory endosome (COSE): a specialized compartment involved in neuronal morphogenesis, Biol. Cell, 2003, 95, 419–424

    Article  PubMed  CAS  Google Scholar 

  25. Alberts P., Rudge R., Irinopoulou T., Danglot L., Gauthier-Rouviere C., Galli T., Cdc42 and actin control polarized expression of TI-VAMP vesicles to neuronal growth cones and their fusion with the plasma membrane, Mol. Biol. Cell, 2006, 17, 1194–1203

    Article  PubMed  CAS  Google Scholar 

  26. Hernandez-Deviez D., Mackay-Sim A., Wilson J.M., A Role for ARF6 and ARNO in the regulation of endosomal dynamics in neurons, Traffic, 2007, 8, 1750–1764

    Article  PubMed  CAS  Google Scholar 

  27. Levine B., Klionsky D.J., Development by self-digestion: molecular mechanisms and biological functions of autophagy, Dev. Cell, 2004, 6, 463–477

    Article  PubMed  CAS  Google Scholar 

  28. Cecconi F., Bartolomeo S.D., Nardacci R., Fuoco C., Corazzari M., Giunta L., et al., A novel role for autophagyin neurodevelopment, Autophagy, 2007, 3, 506–508

    PubMed  CAS  Google Scholar 

  29. Maria Fimia G., Stoykova A., Romagnoli A., Giunta L., Di Bartolomeo S., Nardacci R., et al., Ambra1 regulates autophagy and development of the nervous system, Nature, 2007, 447, 1121–1125

    Google Scholar 

  30. Nixon R. A., Yang D.S., Lee J.H., Neurodegenerative lysosomal disorders: A continuum from developmente too late age, Autophagy, 2008, 4, 590–599

    PubMed  CAS  Google Scholar 

  31. Filimonenko M., Stuffers S., Raiborg C., Yamamoto A., Malerod L., Fisher E.M., et al., Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease, J. Cell Biol., 2007, 179, 485–500

    Article  PubMed  CAS  Google Scholar 

  32. Lee J.A., Gao F.B., Roles of ESCRT in autophagy-associated neurodegeneration, Autophagy, 2008, 4, 230–232

    PubMed  CAS  Google Scholar 

  33. Parkinson N., Ince P.G., Smith M.O., Highley R., Skibinski G., Andersen P.M., et al., ALS phenotypes with mutations in CHMP2B (charged multivesicular body protein 2B), Neurology, 2006, 67, 1074–1077

    Article  PubMed  CAS  Google Scholar 

  34. Rusten T.E., Filimonenco M., Rodhal L.M., Stenmark H., Simonsen A., ESCRT ing autophagic clearance of aggregating proteins, Autophagy, 2008, 4, 233–236

    CAS  Google Scholar 

  35. Skibinski G., Parkinson N.J., Brown J.M., Chakrabarti L., Lloyd S.L., Hummerich H., et al., Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia, Nat. Genet., 2005, 37, 806–808

    Article  PubMed  CAS  Google Scholar 

  36. Truant R., Atwal R.S., Desmond C., Munsie L., Tran T., Huntington’s disease: revisiting the aggregation hypothesis in polyglutamine neurodegenerative diseases, FEBS J., 2008, 275, 4252–4262

    Article  PubMed  CAS  Google Scholar 

  37. Kidd M., Alzheimer’s disease — an electron microscopical study, Brain, 1964, 87, 307–320

    Article  PubMed  CAS  Google Scholar 

  38. Paula-Barbosa M.M., Mota Cardoso R., Faria R., Cruz C., Multivesicular bodies i cortical dendrites of two patients with Alzheimer’s disease, J. Neurol. Sci., 1978, 36, 259–264

    Article  PubMed  CAS  Google Scholar 

  39. Takahashi R.H., Milner T.A., Li F., Nam E.E., Edgar M.A., Yamaguchi H., et al., Intraneuronal Alzheimer abeta42 accumulates in multivesicular bodies and is associated with synaptic pathology, Am. J. Pathol., 2002, 161, 1869–1879

    Article  PubMed  CAS  Google Scholar 

  40. Nixon R.A., Yang D.-S., Autophagy failure in Alzheimer’s diseaselocating the primary defect, Neurobiol. Dis., 2011, 43, 38–45

    Article  PubMed  CAS  Google Scholar 

  41. Winslow A.R., Chen C.W., Corrochiano S., Acevedo-Arozena A., Gordon D.E., et al., Alpha-synuclein impairs macroautophagy: implications for Parkinson’s disease, J.Cell Biol., 2010, 190, 1023–1037

    Article  PubMed  CAS  Google Scholar 

  42. Webb J.L., Ravikumar B., Atkins J., Skepper J.N., Rubinsztein D.C., Alpha-synuclein is degraded by both autophagy and the proteasome, J. Biol. Chem., 2003, 278, 25009–13

    Article  PubMed  CAS  Google Scholar 

  43. Cuervo A.M., Stefanis L., Fredenburg R., Lansbury P.T., Sulzer D., Impaired degradation of mutant alpha-synuclein by chaperonemediated autophagy, Science, 2004, 305, 1292–1295

    Article  PubMed  CAS  Google Scholar 

  44. Vogiatzi T., Xilouri M., Vekrellis K., Stefanis L., Wild thype alphasynuclein is degraded by chaperone-mediated autophagy and macroautophagy in neuronal cells, J. Biol. Chem., 2008, 283, 23542–23556

    Article  PubMed  CAS  Google Scholar 

  45. Anglade P., Vyas S., Javoy-Agid F., Herrero M.T., Michel P.P., Marquez J., et al., Apoptosis and autophagy in nigral neurons of patients with Parkinson’s disease, Histol. Histopathol., 1997, 12, 25–31

    PubMed  CAS  Google Scholar 

  46. Lee J.A., Beigneux A., Ahmad S.T., Yang S.G., Gao F.B., ESCRTIII dysfunction causes autophagosome accumulation and neurodegeneration, Curr. Biol., 2007, 17, 1561–1567

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Andrea Diana.

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Diana, A. Autophagosomes and multivesicular bodies in neuronal development and degeneration. Translat.Neurosci. 3, 384–387 (2012). https://doi.org/10.2478/s13380-012-0048-3

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  • DOI: https://doi.org/10.2478/s13380-012-0048-3

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