Local Control of Nuclear Calcium Signaling in Cardiac Myocytes by Perinuclear Microdomains of Sarcolemmal Insulin-Like Growth Factor 1 Receptors
Author
dc.contributor.author
Ibarra, Cristián
Author
dc.contributor.author
Vicencio, José M.
es_CL
Author
dc.contributor.author
Estrada Hormazábal, Manuel
es_CL
Author
dc.contributor.author
Lin, Yingbo
es_CL
Author
dc.contributor.author
Rocco, Paola
es_CL
Author
dc.contributor.author
Rebellato, Paola
es_CL
Author
dc.contributor.author
Muñoz, Juan P.
es_CL
Author
dc.contributor.author
García Prieto, Jaime
es_CL
Author
dc.contributor.author
Quest, Andrew F. G.
es_CL
Author
dc.contributor.author
Chiong Lay, Mario
es_CL
Author
dc.contributor.author
Davidson, Sean M.
es_CL
Author
dc.contributor.author
Bulatovic, Ivana
es_CL
Author
dc.contributor.author
Grinnemo, Karl Henrik
es_CL
Author
dc.contributor.author
Larsson, Olle
es_CL
Author
dc.contributor.author
Szabadkai, Gyorgy
es_CL
Author
dc.contributor.author
Uhlén, Per
es_CL
Author
dc.contributor.author
Jaimovich Pérez, Enrique
es_CL
Author
dc.contributor.author
Lavandero González, Sergio
es_CL
Admission date
dc.date.accessioned
2014-02-11T14:07:34Z
Available date
dc.date.available
2014-02-11T14:07:34Z
Publication date
dc.date.issued
2013
Cita de ítem
dc.identifier.citation
Circ Res. 2013;112:236-245
en_US
Identifier
dc.identifier.issn
0009-7330
Identifier
dc.identifier.other
10.1161/CIRCRESAHA.112.273839
Identifier
dc.identifier.uri
https://repositorio.uchile.cl/handle/2250/124102
General note
dc.description
Artículo de publicación ISI
en_US
Abstract
dc.description.abstract
Rationale: The ability of a cell to independently regulate nuclear and cytosolic Ca2+ 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 Ca2+
signals, which allows sarcomere contraction in response to plasma membrane depolarization, but whether there is
a similar structure tunneling extracellular stimulation to control nuclear Ca2+ signals locally has not been explored.
Objective: To study the role of perinuclear sarcolemma in selective nuclear Ca2+ signaling.
Methods and Results: We report here that insulin-like growth factor 1 triggers a fast and independent nuclear Ca2+
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 Ca2+ signaling and transcriptional upregulation
through the perinuclear hydrolysis of phosphatidylinositol 4,5-biphosphate inositol 1,4,5-trisphosphate production,
nuclear Ca2+ release, and activation of the transcription factor myocyte-enhancing factor 2C. Genetically engineered
Ca2+ buffers—parvalbumin—with cytosolic or nuclear localization demonstrated that the nuclear Ca2+ handling
system is physically and functionally segregated from the cytosolic Ca2+ signaling machinery.
Conclusions: These data reveal the existence of an inositol 1,4,5-trisphosphate–dependent nuclear Ca2+ toolkit
located in direct apposition to the cell surface, which allows the local control of rapid and independent activation
of nuclear Ca2+ signaling in response to an extracellular ligand.