Tensin3 interaction with talin drives the formation of fibronectin-associated fibrillar adhesions

被引：11

作者：

Atherton, Paul ^{[1
,2
]}

Konstantinou, Rafaella ^{[1
,3
]}

Neo, Suat Peng ^{[4
]}

Wang, Emily ^{[5
]}

Balloi, Eleonora ^{[1
]}

Ptushkina, Marina ^{[1
]}

Bennett, Hayley ^{[6
]}

Clark, Kath ^{[7
]}

Gunaratne, Jayantha ^{[4
]}

Critchley, David ^{[7
]}

Barsukov, Igor ^{[5
]}

Manser, Edward ^{[3
]}

Ballestrem, Christoph ^{[1
]}

机构：

[1] Univ Manchester, Wellcome Trust, Ctr Cell Matrix Res, Manchester, Lancs, England

[2] Netherlands Canc Inst, Div Cell Biol, Amsterdam, Netherlands

[3] ASTAR, Inst Mol & Cell Biol, sGSK Grp, Singapore, Singapore

[4] ASTAR, Quantitat Prote Grp, Inst Mol & Cell Biol, Singapore, Singapore

[5] Univ Liverpool, Inst Integrat Biol, Liverpool, Merseyside, England

[6] Univ Manchester, Genome Editing Unit, Fac Biol Med & Hlth, Manchester, Lancs, England

[7] Univ Leicester, Dept Biochem, Leicester, Leics, England

来源：

JOURNAL OF CELL BIOLOGY | 2022年 / 221卷 / 10期

基金：

英国惠康基金; 英国生物技术与生命科学研究理事会; 英国工程与自然科学研究理事会;

关键词：

EXTRACELLULAR-MATRIX; FOCAL ADHESIONS; FORCE TRANSMISSION; SH2; DOMAIN; CELL; VINCULIN; REVEALS; BINDING; ACTIVATION; DYNAMICS;

D O I：

10.1083/jcb.202107022

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The formation of healthy tissue involves continuous remodeling of the extracellular matrix (ECM). Whilst it is known that this requires integrin-associated cell-ECM adhesion sites (CMAs) and actomyosin-mediated forces, the underlying mechanisms remain unclear. Here, we examine how tensin3 contributes to the formation of fibrillar adhesions (FBs) and fibronectin fibrillogenesis. Using BioID mass spectrometry and a mitochondrial targeting assay, we establish that tensin3 associates with the mechanosensors such as talin and vinculin. We show that the talin R11 rod domain binds directly to a helical motif within the central intrinsically disordered region (IDR) of tensin3, whilst vinculin binds indirectly to tensin3 via talin. Using CRISPR knock-out cells in combination with defined tensin3 mutations, we show (i) that tensin3 is critical for the formation of alpha 5 beta 1-integrin FBs and for fibronectin fibrillogenesis, and (ii) the talin/tensin3 interaction drives this process, with vinculin acting to potentiate it.

引用

页数：26

共 66 条

[41] The myofibroblast at a glance [J].