PPP2R1A regulates migration persistence through the NHSL1-containing WAVE Shell Complex

被引：10

作者：

Wang, Yanan ^{[1
]}

Chiappetta, Giovanni ^{[2
]}

Guerois, Raphael ^{[3
]}

Liu, Yijun ^{[4
]}

Romero, Stephane ^{[1
]}

Boesch, Daniel J. ^{[4
]}

Krause, Matthias ^{[5
]}

Dessalles, Claire A. ^{[6
]}

Babataheri, Avin ^{[6
]}

Barakat, Abdul I. ^{[6
]}

Chen, Baoyu ^{[4
]}

Vinh, Joelle ^{[2
]}

Polesskaya, Anna ^{[1
]}

Gautreau, Alexis M. ^{[1
]}

机构：

[1] Inst Polytech Paris, Ecole Polytech, Lab Struct Biol theCell BIOC, CNRS,UMR7654, F-91120 Palaiseau, France

[2] Univ PSL, ESPCI Paris, Biol Mass Spectrometry & Prote SMBP, LPC,CNRS,UMR8249, F-75005 Paris, France

[3] Univ Paris Saclay, CNRS, Inst Integrat Biol Cell I2BC, CEA, F-91198 Gif Sur Yvette, France

[4] Iowa State Univ, Roy J Carver Dept Biochem, Biophys & Mol Biol, Ames, IA 50011 USA

[5] Kings Coll London, Randall Ctr Cell & Mol Biophys, New Hunts House,Guys Campus, London SE1 1UL, England

[6] Inst Polytech Paris, Ecole Polytech, LadHyX, F-91120 Palaiseau, France

来源：

NATURE COMMUNICATIONS | 2023年 / 14卷 / 01期

基金：

美国国家卫生研究院;

关键词：

ARP2/3; COMPLEX; CELL-MIGRATION; ACTIN; SCAR/WAVE; POLARITY; RAC1; WASP;

D O I：

10.1038/s41467-023-39276-w

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The RAC1-WAVE-Arp2/3 signaling pathway generates branched actin networks that power lamellipodium protrusion of migrating cells. Feedback is thought to control protrusion lifetime and migration persistence, but its molecular circuitry remains elusive. Here, we identify PPP2R1A by proteomics as a protein differentially associated with the WAVE complex subunit ABI1 when RAC1 is activated and downstream generation of branched actin is blocked. PPP2R1A is found to associate at the lamellipodial edge with an alternative form of WAVE complex, the WAVE Shell Complex, that contains NHSL1 instead of the Arp2/3 activating subunit WAVE, as in the canonical WAVE Regulatory Complex. PPP2R1A is required for persistence in random and directed migration assays and for RAC1-dependent actin polymerization in cell extracts. PPP2R1A requirement is abolished by NHSL1 depletion. PPP2R1A mutations found in tumors impair WAVE Shell Complex binding and migration regulation, suggesting that the coupling of PPP2R1A to the WAVE Shell Complex is essential to its function.

引用

页数：18

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