title: Calmodulin-controlled spatial decoding of oscillatory Ca2+ signals by calcineurin.
abstract: Calcineurin is responsible for mediating a wide variety of cellular processes in response to dynamic calcium (Ca(2+)) signals, yet the precise mechanisms involved in the spatiotemporal control of calcineurin signaling are poorly understood. Here, we use genetically encoded fluorescent biosensors to directly probe the role of cytosolic Ca(2+) oscillations in modulating calcineurin activity dynamics in insulin-secreting MIN6 β-cells. We show that Ca(2+) oscillations induce distinct temporal patterns of calcineurin activity in the cytosol and plasma membrane vs at the ER and mitochondria in these cells. Furthermore, we found that these differential calcineurin activity patterns are determined by variations in the subcellular distribution of calmodulin (CaM), indicating that CaM plays an active role in shaping both the spatial and temporal aspects of calcineurin signaling. Together, our findings provide new insights into the mechanisms by which oscillatory signals are decoded to generate specific functional outputs within different cellular compartments.
authors: Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, United States.
authors: Sohum
authors: S
authors: Mehta
authors: Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, United States.
authors: Nwe-Nwe
authors: NN
authors: Aye-Han
authors: Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, United States.
authors: Ambhighainath
authors: A
authors: Ganesan
authors: Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, United States.
authors: Laurel
authors: L
authors: Oldach
authors: Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, United States.
authors: Kirill
authors: K
authors: Gorshkov
authors: Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, United States The Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, United States Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, United States jzhang32@jhmi.edu.
authors: Jin
authors: J
authors: Zhang
mesh_terms: D000818:Animals; D019703:Calcineurin / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000235:genetics*; D002147:Calmodulin / Q000235:genetics / Q000378:metabolism*; D002451:Cell Compartmentation; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D031541:Fluorescence Resonance Energy Transfer; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
chemical_list: D002147:Calmodulin; C485182:Cyan Fluorescent Protein; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D019703:Calcineurin; D002118:Calcium
keywords: FRET; calcium; live-cell imaging; oscillation