title: Current state of imaging protein-protein interactions in vivo with genetically encoded reporters.
abstract: Signaling pathways regulating proliferation, differentiation, and inflammation are commonly mediated through protein-protein interactions as well as reversible modification (e.g., phosphorylation) of proteins. To facilitate the study of regulated protein-protein interactions in cells and living animals, new imaging tools, many based on optical signals and capable of quantifying protein interactions in vivo, have advanced the study of induced protein interactions and their modification, as well as accelerated the rate of acquisition of these data. In particular, use of protein fragment complementation as a reporter strategy can accurately and rapidly dissect protein interactions with a variety of readouts, including absorbance, fluorescence, and bioluminescence. This review focuses on the development and validation of bioluminescent protein fragment complementation reporters that use either Renilla luciferase or firefly luciferase in vivo. Enhanced luciferase complementation provides a platform for near real-time detection and characterization of regulated and small-molecule-induced protein-protein interactions in intact cells and living animals and enables a wide range of novel applications in drug discovery, chemical genetics, and proteomics research.
authors.affiliation: Molecular Imaging Center, Mallinckrodt Institute of Radiology, and Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110, USA. piwnica-wormsd@mir.wustl.edu
authors.forename: Victor
authors.initials: V
authors.lastname: Villalobos
authors.forename: Snehal
authors.initials: S
authors.lastname: Naik
authors.forename: David
authors.initials: D
authors.lastname: Piwnica-Worms
mesh_terms: D005456:Fluorescent Dyes; D017930:Genes, Reporter / Q000235:genetics*; D008163:Luminescent Measurements / Q000379:methods / Q000639:trends*; D008856:Microscopy, Fluorescence / Q000379:methods / Q000639:trends*; D025941:Protein Interaction Mapping / Q000379:methods / Q000639:trends*; D011993:Recombinant Fusion Proteins / Q000235:genetics*
chemical_list: D005456:Fluorescent Dyes; D011993:Recombinant Fusion Proteins