title: Förster resonance energy transfer - an approach to visualize the spatiotemporal regulation of macromolecular complex formation and compartmentalized cell signaling.
abstract: BACKGROUND
  Signaling messengers and effector proteins provide an orchestrated molecular machinery to relay extracellular signals to the inside of cells and thereby facilitate distinct cellular behaviors. Formations of intracellular macromolecular complexes and segregation of signaling cascades dynamically regulate the flow of a biological process.
  
  
  METHODS
  In this review, we provide an overview of the development and application of FRET technology in monitoring cyclic nucleotide-dependent signalings and protein complexes associated with these signalings in real time and space with brief mention of other important signaling messengers and effector proteins involved in compartmentalized signaling.
  
  
  CONCLUSIONS
  The preciseness, rapidity and specificity of cellular responses indicate restricted alterations of signaling messengers, particularly in subcellular compartments rather than globally. Not only the physical confinement and selective depletion, but also the intra- and inter-molecular interactions of signaling effectors modulate the direction of signal transduction in a compartmentalized fashion. To understand the finer details of various intracellular signaling cascades and crosstalk between proteins and other effectors, it is important to visualize these processes in live cells. Förster Resonance Energy Transfer (FRET) has been established as a useful tool to do this, even with its inherent limitations.
  
  
  CONCLUSIONS
  FRET technology remains as an effective tool for unraveling the complex organization and distribution of various endogenous signaling proteins, as well as the spatiotemporal dynamics of second messengers inside a single cell to distinguish the heterogeneity of cell signaling under normal physiological conditions and during pathological events.
authors.affiliation: Division of Pulmonary Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, MLC2120 3333 Burnet Avenue Cincinnati, OH 45229, USA; Department of Physiology, University of Tennessee Health Science Center, 426 Nash Research Building, 894 Union Avenue, Memphis, TN 38163, USA.
authors.forename: Chandrima
authors.initials: C
authors.lastname: Sinha
authors.affiliation: Division of Pulmonary Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, MLC2120 3333 Burnet Avenue Cincinnati, OH 45229, USA.
authors.forename: Kavisha
authors.initials: K
authors.lastname: Arora
authors.affiliation: Division of Pulmonary Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, MLC2120 3333 Burnet Avenue Cincinnati, OH 45229, USA.
authors.forename: Chang Suk
authors.initials: CS
authors.lastname: Moon
authors.affiliation: Division of Pulmonary Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, MLC2120 3333 Burnet Avenue Cincinnati, OH 45229, USA.
authors.forename: Sunitha
authors.initials: S
authors.lastname: Yarlagadda
authors.affiliation: Division of Pulmonary Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, MLC2120 3333 Burnet Avenue Cincinnati, OH 45229, USA.
authors.forename: Koryse
authors.initials: K
authors.lastname: Woodrooffe
authors.affiliation: Division of Pulmonary Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, MLC2120 3333 Burnet Avenue Cincinnati, OH 45229, USA; Department of Physiology, University of Tennessee Health Science Center, 426 Nash Research Building, 894 Union Avenue, Memphis, TN 38163, USA. Electronic address: anaren@cchmc.org.
authors.forename: Anjaparavanda P
authors.initials: AP
authors.lastname: Naren
mesh_terms: D000818:Animals; D031541:Fluorescence Resonance Energy Transfer / Q000295:instrumentation / Q000379:methods; D006801:Humans; D046912:Multiprotein Complexes / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D046912:Multiprotein Complexes
keywords: Compartmentalized cell signaling; Förster Resonance Energy Transfer (FRET); Macromolecular complex
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