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PPP2R1A Regulates Migration Persistence through the WAVE Shell Complex

Yanan Wang
  • Function : Author
Giovanni Chiappetta
Raphaël Guérois
Stéphane Romero
Matthias Krause
Claire Dessalles
Avin Babataheri
Abdul Barakat
Joelle Vinh
Anna Polesskaya
Alexis Gautreau


Abstract 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. Using proteomics, we identified PPP2R1A among proteins differentially associated with the WAVE complex subunit ABI1 when RAC1 was activated and downstream generation of branched actin was blocked. PPP2R1A was found to associate at the lamellipodial edge with a novel form of WAVE complex, the WAVE Shell Complex (WSC), that contains NHSL1 instead of the Arp2/3 activating subunit WAVE as in the canonical WAVE Regulatory Complex (WRC). PPP2R1A was required for persistence in random and directed migration assays and for RAC1-dependent actin polymerization in cell extracts. PPP2R1A requirement was abolished by NHSL1 depletion. PPP2R1A mutations found in tumors impaired WSC binding and migration regulation, suggesting that this novel function of PPP2R1A is critical for its tumor suppressor activity.

Dates and versions

hal-03823497 , version 1 (21-10-2022)



Yanan Wang, Giovanni Chiappetta, Raphaël Guérois, Stéphane Romero, Matthias Krause, et al.. PPP2R1A Regulates Migration Persistence through the WAVE Shell Complex. 2022. ⟨hal-03823497⟩


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