Tunnelling nanotube formation is driven by Eps8/IRSp53-dependent linear actin polymerization.
actin cytoskeleton
cell biophysics
proteomics
tunnelling nanotubes
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
11 Dec 2023
11 Dec 2023
Historique:
revised:
27
10
2023
received:
13
02
2023
accepted:
02
11
2023
pubmed:
27
11
2023
medline:
27
11
2023
entrez:
27
11
2023
Statut:
ppublish
Résumé
Tunnelling nanotubes (TNTs) connect distant cells and mediate cargo transfer for intercellular communication in physiological and pathological contexts. How cells generate these actin-mediated protrusions to span lengths beyond those attainable by canonical filopodia remains unknown. Through a combination of micropatterning, microscopy, and optical tweezer-based approaches, we demonstrate that TNTs formed through the outward extension of actin achieve distances greater than the mean length of filopodia and that branched Arp2/3-dependent pathways attenuate the extent to which actin polymerizes in nanotubes, thus limiting their occurrence. Proteomic analysis using epidermal growth factor receptor kinase substrate 8 (Eps8) as a positive effector of TNTs showed that, upon Arp2/3 inhibition, proteins enhancing filament turnover and depolymerization were reduced and Eps8 instead exhibited heightened interactions with the inverted Bin/Amphiphysin/Rvs (I-BAR) domain protein IRSp53 that provides a direct connection with linear actin polymerases. Our data reveals how common protrusion players (Eps8 and IRSp53) form tunnelling nanotubes, and that when competing pathways overutilizing such proteins and monomeric actin in Arp2/3 networks are inhibited, processes promoting linear actin growth dominate to favour tunnelling nanotube formation.
Identifiants
pubmed: 38009333
doi: 10.15252/embj.2023113761
pmc: PMC10711657
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e113761Subventions
Organisme : Agence Nationale de la Recherche (ANR)
ID : ANR-17-CONV-0005 Q-LIFE
Organisme : Agence Nationale de la Recherche (ANR)
ID : ANR-20-CE13-0032 LiveTuneL
Organisme : Centre National de la Recherche Scientifique (CNRS)
Organisme : Fondation pour la Recherche Médicale (FRM)
ID : FRM EQU202103012692
Organisme : Pasteur Foundation (The Pasteur Foundation)
Organisme : Sorbonne Université (Sorbonne University)
ID : 2018
Informations de copyright
© 2023 The Authors. Published under the terms of the CC BY 4.0 license.
Références
Curr Opin Cell Biol. 2021 Aug;71:139-147
pubmed: 33866130
J Cell Sci. 2016 Feb 15;129(4):665-72
pubmed: 26823607
Cell Death Dis. 2013 Jul 18;4:e726
pubmed: 23868059
Proc Natl Acad Sci U S A. 2021 Oct 26;118(43):
pubmed: 34686599
Elife. 2015 Aug 21;4:
pubmed: 26295568
EMBO Mol Med. 2020 Dec 7;12(12):e12025
pubmed: 33179866
Lab Chip. 2009 Jun 7;9(11):1640-2
pubmed: 19458875
J Biol Chem. 2001 Jun 22;276(25):23092-6
pubmed: 11340065
Sci Adv. 2021 Mar 26;7(13):
pubmed: 33771860
Cell. 1999 May 28;97(5):599-607
pubmed: 10367889
Cell. 2007 Mar 9;128(5):915-29
pubmed: 17350576
Biophys J. 2005 Aug;89(2):782-95
pubmed: 15879474
Eur J Cell Biol. 2015 Oct;94(10):429-43
pubmed: 26164368
Mol Cell Biol. 2010 Feb;30(3):829-44
pubmed: 19933840
Sci Adv. 2022 Jul 22;8(29):eabo0171
pubmed: 35857849
Sci Signal. 2013 Dec 17;6(306):ra109
pubmed: 24345680
Nat Commun. 2022 Mar 28;13(1):1636
pubmed: 35347113
Biophys J. 2015 Feb 3;108(3):489-97
pubmed: 25650917
Proc Natl Acad Sci U S A. 2017 Nov 14;114(46):E9873-E9882
pubmed: 29078295
Science. 2004 Feb 13;303(5660):1007-10
pubmed: 14963329
Nat Cell Biol. 2011 Sep 02;13(9):1012-3; author reply 1013-4
pubmed: 21892140
Nature. 2020 Sep;585(7823):91-95
pubmed: 32788726
Sci Adv. 2022 Oct 14;8(41):eabp8677
pubmed: 36240267
EMBO J. 2023 Dec 11;42(24):e113761
pubmed: 38009333
Radiat Oncol. 2019 Dec 3;14(1):218
pubmed: 31796110
Dev Cell. 2015 Jan 12;32(1):43-53
pubmed: 25543282
Biophys J. 2011 Jul 6;101(1):43-52
pubmed: 21723813
Mol Cell Biol. 2010 Apr;30(7):1703-17
pubmed: 20123970
Nat Commun. 2015 Oct 15;6:8529
pubmed: 26469246
EMBO J. 2013 Oct 16;32(20):2735-50
pubmed: 24076653
Nat Commun. 2019 Jan 21;10(1):342
pubmed: 30664666
Annu Rev Cell Dev Biol. 2023 Oct 16;39:307-329
pubmed: 37406300
J Cell Biol. 2010 May 17;189(4):619-29
pubmed: 20457765
Bioinformatics. 2006 Aug 15;22(16):1979-87
pubmed: 16777905
Annu Rev Cell Dev Biol. 2018 Oct 6;34:59-84
pubmed: 30074816
Phys Rev Lett. 2018 Apr 6;120(14):148101
pubmed: 29694156
J Cell Sci. 2016 Jul 15;129(14):2829-40
pubmed: 27278019
EMBO J. 2016 Oct 4;35(19):2120-2138
pubmed: 27550960
J Biol Chem. 2012 Feb 10;287(7):4702-14
pubmed: 22179776
Bioinformatics. 2017 Jan 1;33(1):135-136
pubmed: 27605098
Dev Cell. 2017 Sep 11;42(5):498-513.e6
pubmed: 28867487
Nat Commun. 2021 Feb 4;12(1):791
pubmed: 33542237
Nat Cell Biol. 2004 Dec;6(12):1180-8
pubmed: 15558031
Cell. 2002 Jan 25;108(2):233-46
pubmed: 11832213
PLoS Biol. 2019 Jun 10;17(6):e3000317
pubmed: 31181075
Dev Cell. 2015 Jan 12;32(1):54-67
pubmed: 25543281
Sci Rep. 2016 Dec 23;6:39632
pubmed: 28008977
PLoS Biol. 2010 Jun 01;8(6):e1000387
pubmed: 20532239
Nat Commun. 2021 Apr 6;12(1):2058
pubmed: 33824332
J Cell Biol. 2001 Sep 3;154(5):1031-44
pubmed: 11524436
Curr Biol. 2009 Jan 27;19(2):95-107
pubmed: 19150238
Proteomics. 2016 Jan;16(1):29-32
pubmed: 26572953
Trends Cell Biol. 2021 Feb;31(2):130-142
pubmed: 33309107
Cell Res. 2010 Jan;20(1):72-88
pubmed: 19770844
Curr Biol. 2007 Jan 9;17(1):79-84
pubmed: 17208190
Curr Biol. 2018 Sep 24;28(18):2876-2888.e4
pubmed: 30197089
Nature. 2000 Dec 7;408(6813):732-5
pubmed: 11130076
J Cell Biol. 2003 Feb 3;160(3):399-407
pubmed: 12566430
Nature. 1999 Sep 16;401(6750):290-3
pubmed: 10499589
Nat Rev Mol Cell Biol. 2016 Dec;17(12):799-810
pubmed: 27625321
Curr Biol. 2020 Jul 20;30(14):2651-2664.e5
pubmed: 32470361
EMBO J. 2018 Jan 4;37(1):102-121
pubmed: 29141912
Nature. 2000 Nov 16;408(6810):374-7
pubmed: 11099046
Nucleic Acids Res. 2021 Jan 8;49(D1):D605-D612
pubmed: 33237311
Nat Protoc. 2016 Dec;11(12):2301-2319
pubmed: 27809316
Nat Commun. 2015 May 21;6:7202
pubmed: 25995115
J Neurosci. 2005 Jan 26;25(4):869-79
pubmed: 15673667
Mol Biol Cell. 2013 Nov;24(21):3381-92
pubmed: 23985317
Nat Cell Biol. 2006 Dec;8(12):1337-47
pubmed: 17115031
J Biol Chem. 2008 Jul 18;283(29):20454-72
pubmed: 18448434
Proc Natl Acad Sci U S A. 2013 Nov 19;110(47):18928-33
pubmed: 24198333
Open Biol. 2016 Jun;6(6):
pubmed: 27278648
J Immunol. 2004 Aug 1;173(3):1511-3
pubmed: 15265877
Cancer Res. 2013 Nov 15;73(22):6793-803
pubmed: 24242070
EMBO Rep. 2021 Nov 4;22(11):e53732
pubmed: 34494703
Cell. 2021 Sep 30;184(20):5089-5106.e21
pubmed: 34555357
J Cell Biol. 2008 Mar 10;180(5):887-95
pubmed: 18316411
Proc Natl Acad Sci U S A. 2010 Oct 5;107(40):17194-9
pubmed: 20855598
EMBO J. 2021 Nov 15;40(22):e107264
pubmed: 34494680
Nat Nanotechnol. 2022 Jan;17(1):98-106
pubmed: 34795441
Curr Biol. 2014 Mar 3;24(5):579-85
pubmed: 24560576
Mol Biol Cell. 2020 Dec 1;31(25):2803-2815
pubmed: 33026933
Cytoskeleton (Hoboken). 2013 Jul;70(7):360-84
pubmed: 23749648
J Cell Biol. 2019 Jun 3;218(6):1972-1993
pubmed: 31076452
Cytoskeleton (Hoboken). 2016 Jun;73(7):365-74
pubmed: 27169557
Nucleic Acids Res. 2022 Jan 7;50(D1):D543-D552
pubmed: 34723319
PLoS Comput Biol. 2011 Jul;7(7):e1002088
pubmed: 21814501
J Neurosci. 2003 Feb 15;23(4):1310-9
pubmed: 12598619
Stat Appl Genet Mol Biol. 2004;3:Article3
pubmed: 16646809
Nat Cell Biol. 2008 Feb;10(2):211-9
pubmed: 18193035
Biophys J. 2022 Jun 21;121(12):2436-2448
pubmed: 35598045
Curr Biol. 2000 Nov 16;10(22):1420-6
pubmed: 11102803
Chem Biol. 2013 May 23;20(5):701-12
pubmed: 23623350
J Cell Biol. 2019 Jan 7;218(1):350-379
pubmed: 30523041
Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9083-8
pubmed: 10430899
Nat Rev Mol Cell Biol. 2008 Jun;9(6):446-54
pubmed: 18464790
Nat Cell Biol. 2016 Jan;18(1):76-86
pubmed: 26655834
Curr Biol. 2020 Mar 9;30(5):767-778.e5
pubmed: 32037094
Cell Death Differ. 2015 Jul;22(7):1181-91
pubmed: 25571977
Mol Biol Cell. 2019 May 15;30(11):1285-1297
pubmed: 30893014
Biophys J. 2008 May 15;94(10):3839-52
pubmed: 18234810