title: Rapid and orthogonal logic gating with a gibberellin-induced dimerization system.
abstract: Using a newly synthesized gibberellin analog containing an acetoxymethyl group (GA(3)-AM) and its binding proteins, we developed an efficient chemically inducible dimerization (CID) system that is completely orthogonal to existing rapamycin-mediated protein dimerization. Combining the two systems should allow applications that have been difficult or impossible with only one CID system. By using both chemical inputs (rapamycin and GA(3)-AM), we designed and synthesized Boolean logic gates in living mammalian cells. These gates produced output signals such as fluorescence and membrane ruffling on a timescale of seconds, substantially faster than earlier intracellular logic gates. The use of two orthogonal dimerization systems in the same cell also allows for finer modulation of protein perturbations than is possible with a single dimerizer.
authors.affiliation: Department of Cell Biology, Center for Cell Dynamics, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Miyamoto
authors.forename: Robert
authors.initials: R
authors.lastname: DeRose
authors.forename: Allison
authors.initials: A
authors.lastname: Suarez
authors.forename: Tasuku
authors.initials: T
authors.lastname: Ueno
authors.forename: Melinda
authors.initials: M
authors.lastname: Chen
authors.forename: Tai-ping
authors.initials: TP
authors.lastname: Sun
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Wolfgang
authors.forename: Chandrani
authors.initials: C
authors.lastname: Mukherjee
authors.forename: David J
authors.initials: DJ
authors.lastname: Meyers
authors.forename: Takanari
authors.initials: T
authors.lastname: Inoue
mesh_terms: D000818:Animals; D005453:Fluorescence; D005875:Gibberellins / Q000737:chemistry* / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D055503:Protein Multimerization / Q000187:drug effects*; D020123:Sirolimus / Q000737:chemistry
chemical_list: D005875:Gibberellins; D020123:Sirolimus