title: Local control of nuclear calcium signaling in cardiac myocytes by perinuclear microdomains of sarcolemmal insulin-like growth factor 1 receptors.
abstract: BACKGROUND
  The ability of a cell to independently regulate nuclear and cytosolic Ca(2+) signaling is currently attributed to the differential distribution of inositol 1,4,5-trisphosphate receptor channel isoforms in the nucleoplasmic versus the endoplasmic reticulum. In cardiac myocytes, T-tubules confer the necessary compartmentation of Ca(2+) signals, which allows sarcomere contraction in response to plasma membrane depolarization, but whether there is a similar structure tunneling extracellular stimulation to control nuclear Ca(2+) signals locally has not been explored.
  
  
  OBJECTIVE
  To study the role of perinuclear sarcolemma in selective nuclear Ca(2+) signaling.
  
  
  RESULTS
  We report here that insulin-like growth factor 1 triggers a fast and independent nuclear Ca(2+) signal in neonatal rat cardiac myocytes, human embryonic cardiac myocytes, and adult rat cardiac myocytes. This fast and localized response is achieved by activation of insulin-like growth factor 1 receptor signaling complexes present in perinuclear invaginations of the plasma membrane. The perinuclear insulin-like growth factor 1 receptor pool connects extracellular stimulation to local activation of nuclear Ca(2+) signaling and transcriptional upregulation through the perinuclear hydrolysis of phosphatidylinositol 4,5-biphosphate inositol 1,4,5-trisphosphate production, nuclear Ca(2+) release, and activation of the transcription factor myocyte-enhancing factor 2C. Genetically engineered Ca(2+) buffers--parvalbumin--with cytosolic or nuclear localization demonstrated that the nuclear Ca(2+) handling system is physically and functionally segregated from the cytosolic Ca(2+) signaling machinery.
  
  
  CONCLUSIONS
  These data reveal the existence of an inositol 1,4,5-trisphosphate-dependent nuclear Ca(2+) toolkit located in direct apposition to the cell surface, which allows the local control of rapid and independent activation of nuclear Ca(2+) signaling in response to an extracellular ligand.
authors.affiliation: Centro de Estudios Moleculares de la Célula, Facultad de Ciencias Quimicas y Farmaceuticas, Universidad de Chile, Santiago, Chile.
authors.forename: Cristian
authors.initials: C
authors.lastname: Ibarra
authors.forename: Jose M
authors.initials: JM
authors.lastname: Vicencio
authors.forename: Manuel
authors.initials: M
authors.lastname: Estrada
authors.forename: Yingbo
authors.initials: Y
authors.lastname: Lin
authors.forename: Paola
authors.initials: P
authors.lastname: Rocco
authors.forename: Paola
authors.initials: P
authors.lastname: Rebellato
authors.forename: Juan P
authors.initials: JP
authors.lastname: Munoz
authors.forename: Jaime
authors.initials: J
authors.lastname: Garcia-Prieto
authors.forename: Andrew F G
authors.initials: AF
authors.lastname: Quest
authors.forename: Mario
authors.initials: M
authors.lastname: Chiong
authors.forename: Sean M
authors.initials: SM
authors.lastname: Davidson
authors.forename: Ivana
authors.initials: I
authors.lastname: Bulatovic
authors.forename: Karl-Henrik
authors.initials: KH
authors.lastname: Grinnemo
authors.forename: Olle
authors.initials: O
authors.lastname: Larsson
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Szabadkai
authors.forename: Per
authors.initials: P
authors.lastname: Uhlén
authors.forename: Enrique
authors.initials: E
authors.lastname: Jaimovich
authors.forename: Sergio
authors.initials: S
authors.lastname: Lavandero
mesh_terms: D000328:Adult; D000818:Animals; D000831:Animals, Newborn; D020013:Calcium Signaling / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D006801:Humans; D021962:Membrane Microdomains / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000502:physiology*; D012508:Sarcolemma / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D017526:Receptor, IGF Type 1