A phosphoinositide switch mediates exocyst recruitment to multivesicular endosomes for exosome secretion.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
28 10 2023
28 10 2023
Historique:
received:
02
03
2022
accepted:
17
10
2023
medline:
30
10
2023
pubmed:
29
10
2023
entrez:
29
10
2023
Statut:
epublish
Résumé
Exosomes are secreted to the extracellular milieu when multivesicular endosomes (MVEs) dock and fuse with the plasma membrane. However, MVEs are also known to fuse with lysosomes for degradation. How MVEs are directed to the plasma membrane for exosome secretion rather than to lysosomes is unclear. Here we report that a conversion of phosphatidylinositol-3-phosphate (PI(3)P) to phosphatidylinositol-4-phosphate (PI(4)P) catalyzed sequentially by Myotubularin 1 (MTM1) and phosphatidylinositol 4-kinase type IIα (PI4KIIα) on the surface of MVEs mediates the recruitment of the exocyst complex. The exocyst then targets the MVEs to the plasma membrane for exosome secretion. We further demonstrate that disrupting PI(4)P generation or exocyst function blocked exosomal secretion of Programmed death-ligand 1 (PD-L1), a key immune checkpoint protein in tumor cells, and led to its accumulation in lysosomes. Together, our study suggests that the PI(3)P to PI(4)P conversion on MVEs and the recruitment of the exocyst direct the exocytic trafficking of MVEs for exosome secretion.
Identifiants
pubmed: 37898620
doi: 10.1038/s41467-023-42661-0
pii: 10.1038/s41467-023-42661-0
pmc: PMC10613218
doi:
Substances chimiques
phosphatidylinositol 3-phosphate
0
Phosphatidylinositols
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6883Subventions
Organisme : NIGMS NIH HHS
ID : R35 GM140832
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA261608
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM141832
Pays : United States
Informations de copyright
© 2023. The Author(s).
Références
Dev Cell. 2010 May 18;18(5):828-40
pubmed: 20493815
Science. 2014 Oct 31;346(6209):1256898
pubmed: 25359980
Cell Death Differ. 2019 May;26(5):781-793
pubmed: 30742090
Brain. 2020 Jun 1;143(6):1780-1797
pubmed: 32428221
Dev Cell. 2023 Feb 27;58(4):320-334.e8
pubmed: 36800996
J Cell Biol. 2014 Apr 14;205(1):113-26
pubmed: 24711504
Nat Methods. 2018 May;15(5):367-369
pubmed: 29630062
Mol Cell. 2018 Sep 6;71(5):653-673
pubmed: 30193094
Cell Res. 2018 Aug;28(8):862-864
pubmed: 29959401
Nature. 2016 Jan 21;529(7586):408-12
pubmed: 26760201
Nat Chem Biol. 2010 Jul;6(7):507-13
pubmed: 20559318
Nat Cell Biol. 2010 Jan;12(1):19-30; sup pp 1-13
pubmed: 19966785
J Biol Chem. 2006 Jun 16;281(24):16740-9
pubmed: 16606619
EMBO J. 2020 Aug 17;39(16):e103009
pubmed: 32720716
Nat Chem Biol. 2018 Aug;14(8):801-810
pubmed: 29915378
Cell. 2014 Nov 20;159(5):1027-1041
pubmed: 25416943
Traffic. 2005 Feb;6(2):131-43
pubmed: 15634213
Trends Cell Biol. 2023 Aug;33(8):667-681
pubmed: 36737375
J Cell Sci. 2015 Aug 15;128(16):2957-64
pubmed: 26240175
Nat Commun. 2013;4:1553
pubmed: 23462996
J Comput Chem. 2004 Oct;25(13):1605-12
pubmed: 15264254
Nat Commun. 2020 Nov 25;11(1):5987
pubmed: 33239640
Curr Biol. 2019 Jan 7;29(1):R30-R32
pubmed: 30620914
Nat Commun. 2020 Aug 28;11(1):4339
pubmed: 32859909
Annu Rev Cell Dev Biol. 2016 Oct 6;32:143-171
pubmed: 27576122
Cancer Res. 2017 Nov 15;77(22):6253-6266
pubmed: 28827373
J Cell Sci. 2014 Sep 1;127(Pt 17):3745-56
pubmed: 25002402
Science. 2008 Feb 8;319(5864):810-3
pubmed: 18174397
Nature. 2017 Sep 7;549(7670):106-110
pubmed: 28813410
J Cell Biol. 2010 Apr 19;189(2):223-32
pubmed: 20404108
J Extracell Vesicles. 2023 Apr;12(4):e12319
pubmed: 37021404
Nature. 2018 Aug;560(7718):382-386
pubmed: 30089911
J Biol Methods. 2014;1(2):
pubmed: 25606571
Nature. 2015 Nov 19;527(7578):329-35
pubmed: 26524530
J Biol Chem. 2019 Dec 13;294(50):19099-19110
pubmed: 31694916
EMBO Rep. 2007 Mar;8(3):241-6
pubmed: 17330069
Nat Methods. 2012 Jun 28;9(7):676-82
pubmed: 22743772
Dev Cell. 2022 Apr 25;57(8):974-994.e8
pubmed: 35421371
Trends Cell Biol. 2006 Jul;16(7):351-61
pubmed: 16793271
Biochem Biophys Res Commun. 2015 Sep 25;465(3):601-5
pubmed: 26299925
Nat Struct Mol Biol. 2016 Jan;23(1):59-66
pubmed: 26656853
Science. 2020 Feb 7;367(6478):
pubmed: 32029601
Nat Rev Mol Cell Biol. 2018 Apr;19(4):213-228
pubmed: 29339798
J Cell Biol. 2008 Jan 14;180(1):145-58
pubmed: 18195105
Physiol Rev. 2013 Jul;93(3):1019-137
pubmed: 23899561
Nat Chem Biol. 2019 Jan;15(1):42-50
pubmed: 30397328
Nat Cell Biol. 2023 Mar;25(3):415-424
pubmed: 36797475
Proc Natl Acad Sci U S A. 2016 Jan 5;113(1):E41-50
pubmed: 26607451
J Cell Biol. 2015 Oct 12;211(1):27-37
pubmed: 26459596
J Biol Chem. 2004 Oct 8;279(41):43027-34
pubmed: 15292201
Nat Rev Mol Cell Biol. 2022 May;23(5):369-382
pubmed: 35260831
Sci Rep. 2017 Jan 18;7:40766
pubmed: 28098202
Annu Rev Pathol. 2023 Jan 24;18:205-229
pubmed: 36202098
Nature. 2006 Oct 12;443(7112):651-7
pubmed: 17035995
Annu Rev Cell Dev Biol. 2007;23:519-47
pubmed: 17506697
EMBO J. 2013 Feb 6;32(3):324-39
pubmed: 23258225
Traffic. 2012 Jul;13(7):898-907
pubmed: 22420621
Mol Biol Cell. 2014 Nov 15;25(23):3813-22
pubmed: 25232005
Nat Cell Biol. 2019 Jan;21(1):9-17
pubmed: 30602770
Mol Ther Nucleic Acids. 2021 Dec 17;27:535-546
pubmed: 35036064
J Cell Biol. 2018 Mar 5;217(3):1129-1142
pubmed: 29339438
Mol Biol Cell. 2022 May 1;33(5):
pubmed: 35420888
Sci Adv. 2018 Mar 07;4(3):eaar2766
pubmed: 29532035
Nat Rev Mol Cell Biol. 2023 Jul;24(7):454-476
pubmed: 36765164
Annu Rev Cell Dev Biol. 2014;30:255-89
pubmed: 25288114
Nat Commun. 2017 Jan 23;8:14236
pubmed: 28112172
Nature. 2017 Sep 7;549(7670):101-105
pubmed: 28813417
Nat Commun. 2018 Dec 3;9(1):5140
pubmed: 30510181
Curr Biol. 2018 Sep 10;28(17):R922-R925
pubmed: 30205058
Nat Cell Biol. 1999 May;1(1):E17-22
pubmed: 10559876
Biochem Soc Trans. 2006 Nov;34(Pt 5):683-6
pubmed: 17052174
Curr Biol. 2022 Jul 11;32(13):2821-2833.e6
pubmed: 35609603
Nat Commun. 2022 Jul 14;13(1):4078
pubmed: 35835783
Cell. 1998 Dec 11;95(6):847-58
pubmed: 9865702
Cell. 2019 Apr 4;177(2):414-427.e13
pubmed: 30951669
Mol Biol Cell. 2007 Nov;18(11):4483-92
pubmed: 17761530
Nat Struct Mol Biol. 2005 Oct;12(10):879-85
pubmed: 16155582
Nat Methods. 2014 Mar;11(3):313-8
pubmed: 24487583
EMBO J. 2007 Sep 19;26(18):4053-65
pubmed: 17717527
Proc Natl Acad Sci U S A. 2021 Sep 7;118(36):
pubmed: 34470819
Nat Methods. 2020 Sep;17(9):870-872
pubmed: 32814874
Nat Struct Mol Biol. 2018 Feb;25(2):139-146
pubmed: 29335562