CoChat
Sign Up
Cited by 164

The DOI matches its Crossref record; 16 of the 16 references it cites were found in a registry or an index.

Amyloid precursor protein products concentrate in a subset of exosomes specifically endocytosed by neurons.

Laulagnier, Karine, Javalet, Charlotte, Hemming, Fiona J., Chivet, Mathilde, Lachenal, Gaëlle, Blot, Béatrice, Chatellard, Christine, Sadoul, Rémy·2018·Cellular and Molecular Life Sciences
DOI 10.1007/s00018-017-2664-0
Open this paper in CoChat — free account

Abstract

Amyloid beta peptide (Aβ), the main component of senile plaques of Alzheimer's disease brains, is produced by sequential cleavage of amyloid precursor protein (APP) and of its C-terminal fragments (CTFs). An unanswered question is how amyloidogenic peptides spread throughout the brain during the course of the disease. Here, we show that small lipid vesicles called exosomes, secreted in the extracellular milieu by cortical neurons, carry endogenous APP and are strikingly enriched in CTF-α and the newly characterized CTF-η. Exosomes from N2a cells expressing human APP with the autosomal dominant Swedish mutation contain Aβ peptides as well as CTF-α and CTF-η, while those from cells expressing the non-mutated form of APP only contain CTF-α and CTF-η. APP and CTFs are sorted into a subset of exosomes which lack the tetraspanin CD63 and specifically bind to dendrites of neurons, unlike exosomes carrying CD63 which bind to both neurons and glial cells. Thus, neuroblastoma cells secrete distinct populations of exosomes carrying different cargoes and targeting specific cell types. APP-carrying exosomes can be endocytosed by receiving cells, allowing the processing of APP acquired by exosomes to give rise to the APP intracellular domain (AICD). Thus, our results show for the first time that neuronal exosomes may indeed act as vehicles for the intercellular transport of APP and its catabolites.

Overview

Integrity signals

Registry

Crossref · 10.1007/s00018-017-2664-0

Cites

16 of 16 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

Flagged first, then by citations

Show all 16 references

Research works printed but not linked: 56

  1. Gruenberg J, Stenmark H (2004) The biogenesis of multivesicular endosomes. Nat Rev Mol Cell Biol 5:317–323. doi: 10.1038/nrm1360 · DOI
  2. Denzer K, Kleijmeer MJ, Heijnen HF et al (2000) Exosome: from internal vesicle of the multivesicular body to intercellular signaling device. J Cell Sci 113:3365–3374 · DOI
  3. Laulagnier K, Schieber NL, Maritzen T et al (2011) Role of AP1 and Gadkin in the traffic of secretory endo-lysosomes. Mol Biol Cell 22:2068–2082. doi: 10.1091/mbc.E11-03-0193 · DOI
  4. White IJ, Bailey LM, Aghakhani MR et al (2006) EGF stimulates annexin 1-dependent inward vesiculation in a multivesicular endosome subpopulation. EMBO J 25:1–12. doi: 10.1038/sj.emboj.7600759 · DOI
  5. Subra C, Laulagnier K, Perret B, Record M (2007) Exosome lipidomics unravels lipid sorting at the level of multivesicular bodies. Biochimie 89:205–212. doi: 10.1016/j.biochi.2006.10.014 · DOI
  6. Trajkovic K, Hsu C, Chiantia S et al (2008) Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science 319:1244–1247. doi: 10.1126/science.1153124 · DOI
  7. Colombo M, Raposo G, Théry C (2014) Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol 30:255–289. doi: 10.1146/annurev-cellbio-101512-122326 · DOI · Paper page
  8. Nanbo A, Kawanishi E, Yoshida R, Yoshiyama H (2013) Exosomes derived from Epstein-Barr virus-infected cells are internalized via caveola-dependent endocytosis and promote phenotypic modulation in target cells. J Virol 87:10334–10347. doi: 10.1128/JVI.01310-13 · DOI
  9. Valadi H, Ekström K, Bossios A et al (2007) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9:654–659. doi: 10.1038/ncb1596 · DOI · Paper page
  10. Perez-Gonzalez R, Gauthier SA, Kumar A, Levy E (2012) The exosome secretory pathway transports amyloid precursor protein carboxyl-terminal fragments from the cell into the brain extracellular space. J Biol Chem 287:43108–43115. doi: 10.1074/jbc.M112.404467 · DOI
  11. Street JM, Barran PE, Mackay CL et al (2012) Identification and proteomic profiling of exosomes in human cerebrospinal fluid. J Transl Med 10:5. doi: 10.1186/1479-5876-10-5 · DOI
  12. Fitzner D, Schnaars M, van Rossum D et al (2011) Selective transfer of exosomes from oligodendrocytes to microglia by macropinocytosis. J Cell Sci 124:447–458. doi: 10.1242/jcs.074088 · DOI · Paper page
  13. Wang G, Dinkins M, He Q et al (2012) Astrocytes secrete exosomes enriched with proapoptotic ceramide and prostate apoptosis response 4 (PAR-4): potential mechanism of apoptosis induction in Alzheimer disease (AD). J Biol Chem 287:21384–21395. doi: 10.1074/jbc.M112.340513 · DOI
  14. Chivet M, Hemming F, Pernet-Gallay K et al (2012) Emerging role of neuronal exosomes in the central nervous system. Front Physiol 3:145. doi: 10.3389/fphys.2012.00145 · DOI
  15. Chivet M, Javalet C, Hemming F et al (2013) Exosomes as a novel way of interneuronal communication. Biochem Soc Trans 41:241–244. doi: 10.1042/BST20120266 · DOI
  16. Lachenal G, Pernet-Gallay K, Chivet M et al (2011) Release of exosomes from differentiated neurons and its regulation by synaptic glutamatergic activity. Mol Cell Neurosci 46:409–418. doi: 10.1016/j.mcn.2010.11.004 · DOI
  17. Chivet M, Javalet C, Laulagnier K et al (2014) Exosomes secreted by cortical neurons upon glutamatergic synapse activation specifically interact with neurons. J Extracell Vesicles 3:24722. doi: 10.3402/jev.v3.24722 · DOI · Paper page
  18. Février B, Vilette D, Laude H, Raposo G (2005) Exosomes: a bubble ride for prions? Traffic 6:10–17. doi: 10.1111/j.1600-0854.2004.00247.x · DOI
  19. Haass C, Kaether C, Thinakaran G, Sisodia S (2012) Trafficking and proteolytic processing of APP. Cold Spring Harb Perspect Med 2:a006270. doi: 10.1101/cshperspect.a006270 · DOI · Paper page
  20. Xu W, Weissmiller AM, White JA et al (2016) Amyloid precursor protein–mediated endocytic pathway disruption induces axonal dysfunction and neurodegeneration. J Clin Invest 126:1815–1833. doi: 10.1172/JCI82409 · DOI
  21. Kim S, Sato Y, Mohan PS et al (2016) Evidence that the rab5 effector APPL1 mediates APP-βCTF-induced dysfunction of endosomes in Down syndrome and Alzheimer’s disease. Mol Psychiatry 21:707–716. doi: 10.1038/mp.2015.97 · DOI · Paper page
  22. Baranger K, Marchalant Y, Bonnet AE et al (2016) MT5-MMP is a new pro-amyloidogenic proteinase that promotes amyloid pathology and cognitive decline in a transgenic mouse model of Alzheimer’s disease. Cell Mol Life Sci 73:217–236. doi: 10.1007/s00018-015-1992-1 · DOI · Paper page
  23. Das U, Scott DA, Ganguly A et al (2013) Activity-induced convergence of APP and BACE-1 in acidic microdomains via an endocytosis-dependent pathway. Neuron 79:447–460. doi: 10.1016/j.neuron.2013.05.035 · DOI
  24. Takahashi RH, Milner TA, Li F et al (2002) Intraneuronal Alzheimer abeta42 accumulates in multivesicular bodies and is associated with synaptic pathology. Am J Pathol 161:1869–1879 · DOI · Paper page
  25. Sannerud R, Esselens C, Ejsmont P et al (2016) Restricted location of PSEN2/γ-secretase determines substrate specificity and generates an intracellular Aβ pool. Cell 166:193–208. doi: 10.1016/j.cell.2016.05.020 · DOI · Paper page
  26. Rajendran L, Honsho M, Zahn TR et al (2006) Alzheimer’s disease beta-amyloid peptides are released in association with exosomes. Proc Natl Acad Sci USA 103:11172–11177. doi: 10.1073/pnas.0603838103 · DOI · Paper page
  27. Vingtdeux V, Hamdane M, Loyens A et al (2007) Alkalizing drugs induce accumulation of amyloid precursor protein by-products in luminal vesicles of multivesicular bodies. J Biol Chem 282:18197–18205. doi: 10.1074/jbc.M609475200 · DOI
  28. Sharples RA, Vella LJ, Nisbet RM et al (2008) Inhibition of gamma-secretase causes increased secretion of amyloid precursor protein C-terminal fragments in association with exosomes. FASEB J 22:1469–1478. doi: 10.1096/fj.07-9357com · DOI
  29. Belly A, Bodon G, Blot B et al (2010) CHMP2B mutants linked to frontotemporal dementia impair maturation of dendritic spines. J Cell Sci 123:2943–2954. doi: 10.1242/jcs.068817 · DOI
  30. Chatellard-Causse C, Blot B, Cristina N et al (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. doi: 10.1074/jbc.M204019200 · DOI
  31. Laulagnier K, Javalet C, Hemming FJ, Sadoul R (2017) Purification and analysis of exosomes released by mature cortical neurons following synaptic activation. Methods Mol Biol 1545:129–138. doi: 10.1007/978-1-4939-6728-5_9 · DOI
  32. Schagger H (2006) Tricine-SDS-PAGE. Nat Protoc 1:16–22. doi: 10.1038/nprot.2006.4 · DOI
  33. Bolte S, Cordelières FP (2006) A guided tour into subcellular colocalization analysis in light microscopy. J Microsc 224:213–232. doi: 10.1111/j.1365-2818.2006.01706.x · DOI
  34. Hoey SE, Williams RJ, Perkinton MS (2009) Synaptic NMDA receptor activation stimulates alpha-secretase amyloid precursor protein processing and inhibits amyloid-beta production. J Neurosci 29:4442–4460. doi: 10.1523/JNEUROSCI.6017-08.2009 · DOI · Paper page
  35. Forman MS, Cook DG, Leight S et al (1997) Differential effects of the swedish mutant amyloid precursor protein on β-amyloid accumulation and secretion in neurons and nonneuronal cells. J Biol Chem 272:32247–32253. doi: 10.1074/jbc.272.51.32247 · DOI
  36. Huotari J, Helenius A (2011) Endosome maturation. EMBO J 30:3481–3500. doi: 10.1038/emboj.2011.286 · DOI
  37. Stenmark H, Parton RG, Steele-Mortimer O et al (1994) Inhibition of rab5 GTPase activity stimulates membrane fusion in endocytosis. EMBO J 13:1287–1296 · DOI · Paper page
  38. Cao X, Südhof TC (2004) Dissection of amyloid-beta precursor protein-dependent transcriptional transactivation. J Biol Chem 279:24601–24611. doi: 10.1074/jbc.M402248200 · DOI
  39. Sullivan CP, Jay AG, Stack EC et al (2011) Retromer disruption promotes amyloidogenic APP processing. Neurobiol Dis 43:338–345. doi: 10.1016/j.nbd.2011.04.002 · DOI
  40. Langui D, Girardot N, El Hachimi KH et al (2004) Subcellular topography of neuronal Abeta peptide in APPxPS1 transgenic mice. Am J Pathol 165:1465–1477 · DOI · Paper page
  41. Hoey SE, Buonocore F, Cox CJ et al (2013) AMPA receptor activation promotes non-amyloidogenic amyloid precursor protein processing and suppresses neuronal amyloid-β production. PLoS One 8:e78155. doi: 10.1371/journal.pone.0078155 · DOI
  42. Lesné S, Ali C, Gabriel C et al (2005) NMDA receptor activation inhibits alpha-secretase and promotes neuronal amyloid-beta production. J Neurosci 25:9367–9377. doi: 10.1523/JNEUROSCI.0849-05.2005 · DOI
  43. Stoeck A, Keller S, Riedle S et al (2006) A role for exosomes in the constitutive and stimulus-induced ectodomain cleavage of L1 and CD44. Biochem J 393:609–618. doi: 10.1042/BJ20051013 · DOI
  44. Jämsä A, Belda O, Edlund M, Lindström E (2011) BACE-1 inhibition prevents the γ-secretase inhibitor evoked Aβ rise in human neuroblastoma SH-SY5Y cells. J Biomed Sci 18:76. doi: 10.1186/1423-0127-18-76 · DOI
  45. Lu X, Deng Y, Yu D et al (2014) Histone acetyltransferase p300 mediates histone acetylation of PS1 and BACE1 in a cellular model of Alzheimer’s disease. PLoS One 9:e103067. doi: 10.1371/journal.pone.0103067 · DOI
  46. Mucke L, Masliah E, Yu GQ et al (2000) High-level neuronal expression of abeta 1-42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation. J Neurosci 20:4050–4058 · DOI · Paper page
  47. Falker C, Hartmann A, Guett I et al (2016) Exosomal cellular prion protein drives fibrillization of amyloid beta and counteracts amyloid beta-mediated neurotoxicity. J Neurochem 137:88–100. doi: 10.1111/jnc.13514 · DOI
  48. An K, Klyubin I, Kim Y et al (2013) Exosomes neutralize synaptic-plasticity-disrupting activity of Aβ assemblies in vivo. Mol Brain 6:47. doi: 10.1186/1756-6606-6-47 · DOI
  49. Cataldo AM, Peterhoff CM, Troncoso JC et al (2000) Endocytic pathway abnormalities precede amyloid beta deposition in sporadic Alzheimer’s disease and Down syndrome: differential effects of APOE genotype and presenilin mutations. Am J Pathol 157:277–286 · DOI · Paper page
  50. Hollingworth P, Harold D, Sims R et al (2011) Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer’s disease. Nat Genet 43:429–435. doi: 10.1038/ng.803 · DOI · Paper page
  51. Ubelmann F, Burrinha T, Salavessa L et al (2017) Bin1 and CD2AP polarise the endocytic generation of beta-amyloid. EMBO Rep 18:102–122. doi: 10.15252/embr.201642738 · DOI · Paper page
  52. van Niel G, Charrin S, Simoes S et al (2011) The tetraspanin CD63 regulates ESCRT-independent and -dependent endosomal sorting during melanogenesis. Dev Cell 21:708–721. doi: 10.1016/j.devcel.2011.08.019 · DOI · Paper page
  53. Deyts C, Thinakaran G, Parent AT (2016) APP Receptor. To Be or Not To Be. Trends Pharmacol Sci. doi: 10.1016/j.tips.2016.01.005 · DOI
  54. Sisodia SS, Koo EH, Hoffman PN et al (1993) Identification and transport of full-length amyloid precursor proteins in rat peripheral nervous system. J Neurosci 13:3136–3142 · DOI
  55. Wang Y, Ha Y (2004) The X-ray structure of an antiparallel dimer of the human amyloid precursor protein E2 domain. Mol Cell 15:343–353. doi: 10.1016/j.molcel.2004.06.037 · DOI
  56. Le Blanc I, Luyet P-P, Pons V et al (2005) Endosome-to-cytosol transport of viral nucleocapsids. Nat Cell Biol 7:653–664. doi: 10.1038/ncb1269 · DOI

Cited by

Sorted by citations

See all 164

Metadata

Authors
Laulagnier, K., Javalet, C., Hemming, F. J., Chivet, M., Lachenal, G., Blot, B., Chatellard, C., & Sadoul, R.
Venue
Cellular and Molecular Life Sciences
Publisher
Springer Science and Business Media LLC
Published
2017-09-27
Volume
75
Issue
4
Pages
757-773
ISSN
  • 1420-682X
  • 1420-9071
DOI
10.1007/s00018-017-2664-0
Cited by
164
References
16
Language
en
Licence
www.springer.com/tdm (unspecified)
Funders
  • Association France Alzheimer
  • Agence Nationale de la Recherche (MALZ)
  • Fondation Plan Alzheimer
  • Ministère de l'Education Nationale, de l'Enseignement Superieur et de la Recherche

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review