Seminars

Membrane protrusion and ensuing cell migration are powered by Arp2/3-mediated polymerization of branched actin at the cell cortex. The cortical branched actin pathway involves the small GTPase RAC1 and a combinatorial assembly of complexes containing the Arp2/3 activating subunit, WAVE. The RAC1-WAVE-Arp2/3 pathway also controls the decision to enter into a new cell cycle in a manner tightly coupled with cell migration. In line with these effects on cell migration and proliferation, overexpression of cortical branched actin machinery is associated with poor prognosis in cancer patients. To further our mechanistic understanding, we uncovered novel regulators of cell migration interacting with WAVE complexes. Two powerful methods to pinpoint relevant partners among the hundreds of potential partners identified by tandem affinity purification and proteomics will be presented. 

Relevant references
Polesskaya A, Boutillon A, Yang S, Wang Y, Romero S, Liu Y, Lavielle M, Vacher S, Schnitzler A, Molinie N, Fokin AI, GueroisR, Bièche I, Chen B, David NB, Gautreau AM. 2025. Restrained activation of CYFIP2-containing WAVE complexes controls membrane protrusions and cell migration. BioRxiv. In revision at Review Commons. Novikov NM, Gao J, Fokin AI, Rocques N, Chiappetta G, Rysenkova KD, Zea DJ, Polesskaya A, Vinh J, Guerois R, Gautreau AM. 2025. NHSL3 Controls Single and Collective Cell Migration Through Two Distinct Mechanisms. Nat Commun. 16:205. Wang Y, … , Polesskaya A*, Gautreau AM*. 2023. PPP2R1A regulates migration persistence through the NHSL1-containing WAVE shell complex. Nat Commun. 14:3541. Gautreau AM, Fregoso FE, Simanov G, Dominguez R. 2021. Nucleation, Stabilization and Disassembly of Branched Actin Networks. Trends Cell Biol. S0962-8924. Molinie N, Rubtsova SN, …, Bièche I, Gautreau AM. 2019. Cortical branched actin determines cell cycle progression. Cell Res29:432-45.