Soluble 4R0N Tau Abrogates Endocytic Vesicular Dynamics.
Alzheimer’s disease
amyloid precursor protein (APP)
autophagic stress
endocytic dysfunction
endosome dysfunction
soluble 4R0N tau
vesicle tracking
vesicular trafficking
Journal
Frontiers in aging neuroscience
ISSN: 1663-4365
Titre abrégé: Front Aging Neurosci
Pays: Switzerland
ID NLM: 101525824
Informations de publication
Date de publication:
2020
2020
Historique:
received:
25
02
2020
accepted:
18
09
2020
entrez:
30
11
2020
pubmed:
1
12
2020
medline:
1
12
2020
Statut:
epublish
Résumé
Aggregated tau is a hallmark neuropathological feature in numerous neurodegenerative disorders. Previous studies aiming to validate aggregated tau pathology as a pathogenic driver of neurodegeneration in correlation to characteristic behavioral phenotypes have had shortcomings. Although studies on soluble tau pathology have effectively addressed these shortcomings, the role of soluble tau in the molecular pathogenesis of neurodegeneration is not yet unequivocally established. In sporadic Alzheimer's disease (AD), the relevance of soluble tau pathology in endolysosomal dysfunction and autophagic stress, some of the earliest disease manifestations, is unclear. In this study, we report that soluble 4R0N tau overexpression affects the expression levels of certain markers associated with the endolysosomal system and autophagy. Moreover, through live-cell imaging, we found that the vesicular dynamics of early endosomes were affected with respect to spatiotemporal parameters and vesicle maturation. Additionally, we observed the localization of amyloid precursor protein (APP) along the endocytic pathway and found that upon overexpression of soluble 4R0N tau, APP was preferentially localized to the endocytic compartments implicated in the amyloidogenic pathway. Overall, our observations indicate that soluble 4R0N tau abrogates the dynamics of the endolysosomal system, autophagy, and affects the trafficking of APP. Since the amyloidogenic processing of APP occurs during its progression through the endocytic pathway, our results suggest that the generation of amyloid-β (Aβ) might also be modulated.
Identifiants
pubmed: 33250760
doi: 10.3389/fnagi.2020.537712
pmc: PMC7676905
doi:
Types de publication
Journal Article
Langues
eng
Pagination
537712Informations de copyright
Copyright © 2020 Mahendran, Suresh, Garimella and Manjithaya.
Références
Neurodegener Dis. 2010;7(4):265-71
pubmed: 20551691
Nat Neurosci. 2016 Jan;19(1):55-64
pubmed: 26642089
PLoS Genet. 2014 Oct 02;10(10):e1004626
pubmed: 25275521
Elife. 2017 Jan 13;6:
pubmed: 28085665
Neurobiol Aging. 2005 Mar;26(3):373-82
pubmed: 15639316
FEBS Lett. 1994 Jan 10;337(2):135-8
pubmed: 8287967
Mol Psychiatry. 2018 Oct 31;:
pubmed: 30382187
Methods. 2017 Feb 15;115:80-90
pubmed: 27713081
BMC Cell Biol. 2009 Nov 08;10:81
pubmed: 19895707
Science. 2005 Jul 15;309(5733):476-81
pubmed: 16020737
Neurobiol Dis. 2011 Jul;43(1):68-78
pubmed: 21081164
Free Radic Biol Med. 2018 Jan;114:40-51
pubmed: 28988799
Neuron. 2010 Dec 22;68(6):1067-81
pubmed: 21172610
PLoS Genet. 2015 Jun 26;11(6):e1005290
pubmed: 26115514
Nat Neurosci. 2018 Oct;21(10):1370-1379
pubmed: 30250265
J Neurosci. 1996 Oct 1;16(19):6056-64
pubmed: 8815888
J Neuropathol Exp Neurol. 2000 Aug;59(8):733-48
pubmed: 10952063
J Neuropathol Exp Neurol. 2005 Feb;64(2):113-22
pubmed: 15751225
Ann Neurol. 2002 Feb;51(2):182-9
pubmed: 11835374
EMBO J. 2018 Apr 3;37(7):
pubmed: 29472250
J Cell Biol. 1992 Oct;119(1):123-37
pubmed: 1527164
Cold Spring Harb Perspect Med. 2012 Jul;2(7):a006247
pubmed: 22762014
J Biol Chem. 2018 Feb 16;293(7):2408-2421
pubmed: 29259137
J Alzheimers Dis. 2010;22(2):631-9
pubmed: 20847427
Biol Psychiatry. 2010 Nov 15;68(10):885-93
pubmed: 20655510
J Cell Sci. 2004 Jun 1;117(Pt 13):2687-97
pubmed: 15138286
Autophagy. 2016 Dec;12(12):2404-2419
pubmed: 27715386
J Neurochem. 2017 Mar;140(5):703-717
pubmed: 28027395
Neurosci Res. 2006 Mar;54(3):197-201
pubmed: 16406150
J Chem Neuroanat. 2011 Oct;42(2):102-10
pubmed: 21669283
Science. 2017 May 26;356(6340):
pubmed: 28495876
J Neurochem. 1992 Aug;59(2):750-3
pubmed: 1629745
Neuron. 2016 Mar 2;89(5):971-982
pubmed: 26938442
Alzheimers Res Ther. 2013 Oct 29;5(5):53
pubmed: 24171818
J Biol Chem. 2006 Feb 3;281(5):2683-92
pubmed: 16298992
J Cell Biol. 2010 Aug 9;190(3):363-75
pubmed: 20696706
Neuron. 2011 May 12;70(3):410-26
pubmed: 21555069
J Neurosci. 2008 Jan 23;28(4):862-7
pubmed: 18216194
Acta Neuropathol. 2013 Nov;126(5):631-41
pubmed: 23756600
EMBO J. 2018 Oct 15;37(20):
pubmed: 30166454
J Clin Invest. 2008 Jun;118(6):2190-9
pubmed: 18497889
J Cell Sci. 2004 Sep 15;117(Pt 20):4837-48
pubmed: 15340014
Acta Neuropathol. 2006 Oct;112(4):389-404
pubmed: 16906426
Mol Psychiatry. 2016 May;21(5):707-16
pubmed: 26194181
Mol Neurodegener. 2017 Aug 23;12(1):61
pubmed: 28835279
Autophagy. 2007 Sep-Oct;3(5):452-60
pubmed: 17534139
J Biol Chem. 2003 Aug 15;278(33):31261-8
pubmed: 12761223
J Neuropathol Exp Neurol. 2011 Nov;70(11):960-9
pubmed: 22002422
Ann Neurol. 2016 Jan;79(1):110-9
pubmed: 26505746
Alzheimers Res Ther. 2017 Jan 10;9(1):1
pubmed: 28073379
Nat Neurosci. 2019 Jan;22(1):57-64
pubmed: 30559471
Curr Opin Neurol. 2012 Dec;25(6):715-20
pubmed: 23041958
Science. 2007 May 4;316(5825):750-4
pubmed: 17478722
Proc Natl Acad Sci U S A. 1975 May;72(5):1858-62
pubmed: 1057175
J Cell Biol. 1992 Aug;118(3):573-84
pubmed: 1639844
Nature. 1999 Dec 9;402(6762):672-6
pubmed: 10604474
J Biol Chem. 2011 Jul 1;286(26):23063-76
pubmed: 21550980
Trends Genet. 2006 May;22(5):281-9
pubmed: 16567017
Cell. 2010 Aug 6;142(3):387-97
pubmed: 20655099
Acta Neuropathol. 2016 Dec;132(6):875-895
pubmed: 27770234
J Biol Chem. 1995 Oct 13;270(41):24306-14
pubmed: 7592641
Neuron. 2013 Sep 4;79(5):873-86
pubmed: 24012002
Nat Methods. 2012 Jul;9(7):671-5
pubmed: 22930834
Cold Spring Harb Perspect Med. 2012 May;2(5):a006270
pubmed: 22553493
J Cell Biol. 2013 Aug 5;202(3):495-508
pubmed: 23897889
Transl Psychiatry. 2017 Dec 8;7(12):1267
pubmed: 29217824
Am J Pathol. 2008 Aug;173(2):370-84
pubmed: 18535180
Proc Natl Acad Sci U S A. 2006 Jul 25;103(30):11172-7
pubmed: 16837572
Nat Commun. 2017 Aug 17;8(1):275
pubmed: 28819146
Nature. 2010 Apr 22;464(7292):1201-4
pubmed: 20357768
Sci Rep. 2016 Apr 26;6:24997
pubmed: 27112194
Ann Neurol. 1995 Oct;38(4):643-8
pubmed: 7574461