The phosphatidylinositol 3-phosphate-binding protein SNX4 controls ATG9A recycling and autophagy.
Autophagy
Endosome
Phosphoinositide
Recycling
Journal
Journal of cell science
ISSN: 1477-9137
Titre abrégé: J Cell Sci
Pays: England
ID NLM: 0052457
Informations de publication
Date de publication:
10 02 2021
10 02 2021
Historique:
received:
24
06
2020
accepted:
21
12
2020
pubmed:
21
1
2021
medline:
13
7
2021
entrez:
20
1
2021
Statut:
epublish
Résumé
Late endosomes and lysosomes (endolysosomes) receive proteins and cargo from the secretory, endocytic and autophagic pathways. Although these pathways and the degradative processes of endolysosomes are well characterized, less is understood about protein traffic from these organelles. In this study, we demonstrate the direct involvement of the phosphatidylinositol 3-phosphate (PI3P)-binding SNX4 protein in membrane protein recycling from endolysosomes, and show that SNX4 is required for proper autophagic flux. We show that SNX4 mediates recycling of the lipid scramblase ATG9A, which drives expansion of nascent autophagosome membranes, from endolysosomes to early endosomes, from where ATG9A is recycled to the trans-Golgi network in a retromer-dependent manner. Upon siRNA-mediated depletion of SNX4 or the retromer component VPS35, we observed accumulation of ATG9A on endolysosomes and early endosomes, respectively. Moreover, starvation-induced autophagosome biogenesis and autophagic flux were inhibited when SNX4 was downregulated. We propose that proper ATG9A recycling by SNX4 sustains autophagy by preventing exhaustion of the available ATG9A pool.This article has an associated First Person interview with the first author of the paper.
Identifiants
pubmed: 33468622
pii: jcs.250670
doi: 10.1242/jcs.250670
pmc: PMC7888711
pii:
doi:
Substances chimiques
ATG9A protein, human
0
Autophagy-Related Proteins
0
Carrier Proteins
0
Membrane Proteins
0
Phosphatidylinositol Phosphates
0
SNX4 protein, human
0
Sorting Nexins
0
Vesicular Transport Proteins
0
phosphatidylinositol 3-phosphate
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Cancer Research UK
ID : FC001187
Pays : United Kingdom
Organisme : Wellcome Trust
ID : FC001187
Pays : United Kingdom
Organisme : Medical Research Council
ID : FC001187
Pays : United Kingdom
Informations de copyright
© 2021. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interestsThe authors declare no competing or financial interests.
Références
J Cell Sci. 2006 Sep 15;119(Pt 18):3888-900
pubmed: 16940348
Mol Biol Cell. 2012 May;23(10):1860-73
pubmed: 22456507
EMBO J. 2010 Jan 6;29(1):27-40
pubmed: 19893488
J Cell Sci. 2005 Jan 1;118(Pt 1):7-18
pubmed: 15615779
J Cell Biol. 2008 Aug 25;182(4):685-701
pubmed: 18725538
Dev Cell. 2004 Apr;6(4):463-77
pubmed: 15068787
Nat Cell Biol. 2010 Aug;12(8):747-57
pubmed: 20639872
PLoS One. 2009 Aug 06;4(8):e6529
pubmed: 19657394
Trends Cell Biol. 2010 Jun;20(6):355-62
pubmed: 20356743
J Cell Biol. 2012 Jul 23;198(2):219-33
pubmed: 22826123
Nature. 2005 Dec 1;438(7068):590-6
pubmed: 16319878
Nat Rev Mol Cell Biol. 2001 Mar;2(3):211-6
pubmed: 11265251
Cell Death Differ. 2005 Nov;12 Suppl 2:1535-41
pubmed: 16247501
Nat Commun. 2014 May 13;5:3828
pubmed: 24819384
J Cell Biol. 2019 May 6;218(5):1634-1652
pubmed: 30917996
J Cell Sci. 2003 May 15;116(Pt 10):1937-48
pubmed: 12668730
Mol Biol Cell. 2018 Sep 1;29(18):2190-2200
pubmed: 29949447
Nat Struct Mol Biol. 2020 Dec;27(12):1194-1201
pubmed: 33106659
Traffic. 2018 Aug;19(8):578-590
pubmed: 29667289
Nat Rev Mol Cell Biol. 2009 Jul;10(7):458-67
pubmed: 19491929
EMBO J. 2003 Feb 3;22(3):548-57
pubmed: 12554655
J Cell Biol. 2018 May 7;217(5):1623-1632
pubmed: 29511122
Nat Struct Mol Biol. 2020 Dec;27(12):1185-1193
pubmed: 33106658
EMBO J. 2016 Feb 1;35(3):281-301
pubmed: 26711178
J Cell Biol. 2013 Jul 22;202(2):331-49
pubmed: 23878278
Nat Cell Biol. 2010 Sep;12(9):823-30
pubmed: 20811354
Autophagy. 2016;12(1):1-222
pubmed: 26799652
Traffic. 2007 Mar;8(3):297-309
pubmed: 17319803
Science. 2004 Jan 23;303(5657):495-9
pubmed: 14645856
Am J Physiol Cell Physiol. 2011 Apr;300(4):C723-42
pubmed: 21209361
Nat Rev Mol Cell Biol. 2002 Dec;3(12):919-31
pubmed: 12461558
J Cell Biol. 2012 May 28;197(5):659-75
pubmed: 22613832
J Microsc. 2006 Dec;224(Pt 3):213-32
pubmed: 17210054
J Cell Sci. 2016 Oct 15;129(20):3781-3791
pubmed: 27587839
Cell. 2013 Sep 12;154(6):1285-99
pubmed: 24034251
Autophagy. 2011 Jan;7(1):61-73
pubmed: 21068542
Methods Enzymol. 2009;452:47-61
pubmed: 19200875
Autophagy. 2015;11(1):190-1
pubmed: 25629784