Endosomal LC3C-pathway selectively targets plasma membrane cargo for autophagic degradation.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
02 07 2022
02 07 2022
Historique:
received:
28
09
2021
accepted:
17
06
2022
entrez:
2
7
2022
pubmed:
3
7
2022
medline:
8
7
2022
Statut:
epublish
Résumé
Autophagy selectively targets cargo for degradation, yet mechanistic understanding remains incomplete. The ATG8-family plays key roles in autophagic cargo recruitment. Here by mapping the proximal interactome of ATG8-paralogs, LC3B and LC3C, we uncover a LC3C-Endocytic-Associated-Pathway (LEAP) that selectively recruits plasma-membrane (PM) cargo to autophagosomes. We show that LC3C localizes to peripheral endosomes and engages proteins that traffic between PM, endosomes and autophagosomes, including the SNARE-VAMP3 and ATG9, a transmembrane protein essential for autophagy. We establish that endocytic LC3C binds cargo internalized from the PM, including the Met receptor tyrosine kinase and transferrin receptor, and is necessary for their recruitment into ATG9 vesicles targeted to sites of autophagosome initiation. Structure-function analysis identified that LC3C-endocytic localization and engagement with PM-cargo requires the extended carboxy-tail unique to LC3C, the TBK1 kinase, and TBK1-phosphosites on LC3C. These findings identify LEAP as an unexpected LC3C-dependent pathway, providing new understanding of selective coupling of PM signalling with autophagic degradation.
Identifiants
pubmed: 35780247
doi: 10.1038/s41467-022-31465-3
pii: 10.1038/s41467-022-31465-3
pmc: PMC9250516
doi:
Substances chimiques
Microtubule-Associated Proteins
0
SNARE Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
3812Subventions
Organisme : CIHR
ID : 242529
Pays : Canada
Organisme : CIHR
ID : 148423
Pays : Canada
Organisme : CIHR
ID : 143301
Pays : Canada
Informations de copyright
© 2022. The Author(s).
Références
Cell Rep. 2016 Nov 22;17(9):2221-2233
pubmed: 27880899
Nat Struct Mol Biol. 2020 Dec;27(12):1194-1201
pubmed: 33106659
J Immunol. 2015 Apr 15;194(8):3970-83
pubmed: 25780039
Nat Cell Biol. 2011 Dec 04;14(1):51-60
pubmed: 22138575
Cell Rep. 2019 Dec 17;29(12):4053-4068.e6
pubmed: 31851933
Biochim Biophys Acta. 2012 Mar;1820(3):264-81
pubmed: 21968002
Mol Cell. 2019 Jan 3;73(1):166-182.e7
pubmed: 30609389
Blood. 2012 Oct 25;120(17):3555-62
pubmed: 22898604
J Cell Biol. 2012 Jul 23;198(2):219-33
pubmed: 22826123
Mol Biol Cell. 2012 May;23(10):1860-73
pubmed: 22456507
Am J Cancer Res. 2018 Jun 01;8(6):916-931
pubmed: 30034931
Genome Biol. 2011 Jul 27;12(7):226
pubmed: 21867568
Dev Cell. 2006 Jun;10(6):839-50
pubmed: 16740485
J Cell Sci. 2010 Apr 15;123(Pt 8):1306-19
pubmed: 20332103
Science. 2020 Sep 4;369(6508):
pubmed: 32883836
EMBO Rep. 2012 Aug;13(8):733-40
pubmed: 22732841
Trends Cell Biol. 2016 Aug;26(8):624-635
pubmed: 27050762
EMBO Rep. 2020 Jan 7;21(1):e48317
pubmed: 31709703
Nat Methods. 2017 Jun 29;14(7):645-646
pubmed: 28661499
Proc Natl Acad Sci U S A. 1986 Sep;83(17):6445-9
pubmed: 2875458
Cell Discov. 2020 Feb 11;6:6
pubmed: 32047650
Cell. 2019 Jul 25;178(3):536-551.e14
pubmed: 31257024
PLoS One. 2011;6(9):e23971
pubmed: 21931631
EMBO J. 2013 Feb 20;32(4):524-37
pubmed: 23353890
Nat Commun. 2016 Dec 22;7:13889
pubmed: 28004827
EMBO J. 2016 Aug 15;35(16):1779-92
pubmed: 27370208
Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9559-64
pubmed: 8790369
Autophagy. 2015;11(3):439-51
pubmed: 25714487
Nat Commun. 2016 Aug 11;7:12420
pubmed: 27510922
Nat Rev Mol Cell Biol. 2018 Jun;19(6):349-364
pubmed: 29618831
Nat Cell Biol. 2018 Mar;20(3):233-242
pubmed: 29476151
J Cell Biol. 2021 Jul 5;220(7):
pubmed: 33988680
Trends Cell Biol. 2016 Jan;26(1):6-16
pubmed: 26437584
J Cell Biol. 2019 Jan 7;218(1):285-298
pubmed: 30404949
J Cell Sci. 2019 Feb 20;132(5):
pubmed: 30787029
Mol Cell. 2015 Oct 1;60(1):89-104
pubmed: 26431026
Nat Cell Biol. 2011 Jun 05;13(7):827-37
pubmed: 21642981
Dev Cell. 2011 Jun 14;20(6):751-63
pubmed: 21664574
BMC Bioinformatics. 2021 Sep 10;22(1):433
pubmed: 34507520
Oncogene. 2001 May 17;20(22):2761-70
pubmed: 11420688
Autophagy. 2016;12(1):1-222
pubmed: 26799652
Trends Plant Sci. 2017 Mar;22(3):204-214
pubmed: 28038982
J Biol Chem. 2010 Aug 6;285(32):24956-67
pubmed: 20529867
Mol Cell. 2012 Nov 9;48(3):329-42
pubmed: 23022382
Autophagy. 2013 Oct;9(10):1629-30
pubmed: 24004837
Proc Natl Acad Sci U S A. 2016 Apr 12;113(15):4039-44
pubmed: 27035970
Mol Cell Biol. 2005 Nov;25(21):9632-45
pubmed: 16227611
Cancer Cell. 2012 Apr 17;21(4):532-46
pubmed: 22516261
Methods Mol Biol. 2017;1550:115-136
pubmed: 28188527
Int Rev Cell Mol Biol. 2018;336:1-92
pubmed: 29413888
Autophagy. 2015;11(9):1668-87
pubmed: 26208877
Proc Natl Acad Sci U S A. 2017 Dec 12;114(50):E10697-E10706
pubmed: 29180427
Nat Rev Mol Cell Biol. 2009 Sep;10(9):609-22
pubmed: 19696798
Autophagy. 2017 Jan 2;13(1):57-69
pubmed: 27791468
J Cell Sci. 2016 Oct 15;129(20):3781-3791
pubmed: 27587839
Nat Commun. 2020 May 8;11(1):2291
pubmed: 32385243
Nat Commun. 2018 Sep 14;9(1):3744
pubmed: 30218067
Nat Rev Mol Cell Biol. 2015 Aug;16(8):461-72
pubmed: 26177004
Mol Cell. 2019 Oct 17;76(2):268-285
pubmed: 31585693
Matrix Biol. 2021 Jun;100-101:84-98
pubmed: 33454423
Cold Spring Harb Perspect Biol. 2013 Jul 01;5(7):
pubmed: 23818496
Mol Cell. 2017 Nov 16;68(4):786-796.e6
pubmed: 29149599
J Mol Biol. 2016 May 8;428(9 Pt A):1659-80
pubmed: 26953261
Cancer Res. 2013 Jul 15;73(14):4311-22
pubmed: 23704209
Cell. 2013 Sep 12;154(6):1285-99
pubmed: 24034251
Nat Methods. 2011 Jan;8(1):70-3
pubmed: 21131968
Autophagy. 2020 May;16(5):959-961
pubmed: 32065021
Autophagy. 2013 Oct;9(10):1491-9
pubmed: 23884233
Cell Res. 2014 Jan;24(1):58-68
pubmed: 24296784