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Control of SRC molecular dynamics encodes distinct cytoskeletal responses by specifying signaling pathway usage

15 janv. 2021Journal of Cell Science

DOI : 10.1242/jcs.254599

Auteurs

Adèle Kerjouan, Cyril Boyault, Christiane Oddou, Edwige Hiriart-Bryant, Alexei Grichine, Alexandra Kraut, Mylène Pezet, Martial Balland, Eva Faurobert, Isabelle Bonnet, Yohann Coute, Bertrand Fourcade, Corinne Albiges-Rizo, Olivier Destaing

Résumé

ABSTRACT

Upon activation by different transmembrane receptors, the same signaling protein can induce distinct cellular responses. A way to decipher the mechanisms of such pleiotropic signaling activity is to directly manipulate the decision-making activity that supports the selection between distinct cellular responses. We developed an optogenetic probe (optoSRC) to control SRC signaling, an example of a pleiotropic signaling node, and we demonstrated its ability to generate different acto-adhesive structures (lamellipodia or invadosomes) upon distinct spatio-temporal control of SRC kinase activity. The occurrence of each acto-adhesive structure was simply dictated by the dynamics of optoSRC nanoclusters in adhesive sites, which were dependent on the SH3 and Unique domains of the protein. The different decision-making events regulated by optoSRC dynamics induced distinct downstream signaling pathways, which we characterized using time-resolved proteomic and network analyses. Collectively, by manipulating the molecular mobility of SRC kinase activity, these experiments reveal the pleiotropy-encoding mechanism of SRC signaling.

Membres

ISABELLE BONNET

Sorbonne Université