title: Coronin 1B coordinates Arp2/3 complex and cofilin activities at the leading edge.
abstract: Actin filament formation and turnover within the treadmilling actin filament array at the leading edge of migrating cells are interdependent and coupled, but the mechanisms coordinating these two activities are not understood. We report that Coronin 1B interacts simultaneously with Arp2/3 complex and Slingshot (SSH1L) phosphatase, two regulators of actin filament formation and turnover, respectively. Coronin 1B inhibits filament nucleation by Arp2/3 complex and this inhibition is attenuated by phosphorylation of Coronin 1B at Serine 2, a site targeted by SSH1L. Coronin 1B also directs SSH1L to lamellipodia where SSH1L likely regulates Cofilin activity via dephosphorylation. Accordingly, depleting Coronin 1B increases phospho-Cofilin levels, and alters lamellipodial dynamics and actin filament architecture at the leading edge. We conclude that Coronin 1B's coordination of filament formation by Arp2/3 complex and filament turnover by Cofilin is required for effective lamellipodial protrusion and cell migration.
authors.affiliation: Lineberger Comprehensive Cancer Center and Department of Cell and Developmental Biology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Cai
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Marshall
authors.forename: Andrea C
authors.initials: AC
authors.lastname: Uetrecht
authors.forename: Dorothy A
authors.initials: DA
authors.lastname: Schafer
authors.forename: James E
authors.initials: JE
authors.lastname: Bear
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism; D051339:Actin Depolymerizing Factors / Q000378:metabolism*; D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D004330:Drosophila; D004791:Enzyme Inhibitors / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007734:Kymography; D019319:Okadaic Acid / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D034622:RNA Interference; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D054378:Acetogenins
chemical_list: D015107:4-Butyrolactone; D051339:Actin Depolymerizing Factors; D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; D004791:Enzyme Inhibitors; D049452:Green Fluorescent Proteins; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases; D011994:Recombinant Proteins; C438920:coronin acetogenin; D054378:Acetogenins