title: Imaging the spatial dynamics of calmodulin activation during mitosis.
abstract: BACKGROUND
  Calcium is an important and ubiquitous signalling ion. In most cell types, changes in intracellular calcium concentrations are sensed by calmodulin, a signal transduction protein that regulates cell function through its interactions with kinases and phosphatases. Calcium signals show complex spatiotemporal patterning, but little, if anything, is known about the patterns of calmodulin activation inside cells.
  
  
  RESULTS
  We have measured calmodulin activation continuously during mitosis in living cells with a new probe, a fluorescent adduct of calmodulin termed TA-calmodulin. We found that calmodulin was activated locally and episodically in the nucleus and mitotic spindle. The pattern of calmodulin activation was different from the pattern of calcium signals and could not be predicted from the pattern of calcium increase. Calmodulin activation was essential for mitotic progression: both entry into mitosis and exit from mitosis were blocked by a novel peptide that bound to calmodulin with high affinity and so prevented the interaction of calmodulin with its target proteins.
  
  
  CONCLUSIONS
  These data suggest that calmodulin regulates mitotic transitions and demonstrate the utility of fluorescent adducts for studying protein activation in living cells with good temporal and spatial resolution.
authors.affiliation: Department of Physiological Sciences, University of Newcastle, Medical School, Newcastle upon Tyne, UK.
authors.forename: K
authors.initials: K
authors.lastname: Török
authors.forename: M
authors.initials: M
authors.lastname: Wilding
authors.forename: L
authors.initials: L
authors.lastname: Groigno
authors.forename: R
authors.initials: R
authors.lastname: Patel
authors.forename: M
authors.initials: M
authors.lastname: Whitaker
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000502:physiology; D007091:Image Processing, Computer-Assisted; D008938:Mitosis / Q000502:physiology*; D012617:Sea Urchins; D008941:Spindle Apparatus / Q000378:metabolism / Q000502:physiology
chemical_list: D002147:Calmodulin; C090205:calmodulin, 2-chloro-(epsilon-amino-lysine(75))-(6-(4-(N,N-diethylamino)phenyl)-1,3,5-triazin-4-yl)-; D002118:Calcium