Mid-range Ca2+ signalling mediated by functional coupling between store-operated Ca2+ entry and IP3-dependent Ca2+ release

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Abstract

The versatility and universality of Ca2+ signals stem from the breadth of their spatial and temporal dynamics. Spatially, Ca2+ signalling is well studied in the microdomain scale, close to a Ca2+ channel, and at the whole-cell level. However, little is known about how local Ca2+ signals are regulated to specifically activate spatially distant effectors without a global Ca2+ rise. Here we show that an intricate coupling between the inositol 1,4,5 trisphosphate (IP3) receptor, SERCA pump and store-operated Ca2+ entry (SOCE) allows for efficient mid-range Ca2+ signalling. Ca2+ flowing through SOCE is taken up into the ER lumen by the SERCA pump, only to be re-released by IP 3Rs to activate distal Ca2+-activated Cl- channels (CaCCs). This CaCC regulation contributes to setting the membrane potential of the cell. Hence functional coupling between SOCE, SERCA and IP 3R limits local Ca2+ diffusion and funnels Ca2+ through the ER lumen to activate a spatially separate Ca2+ effector.

Original languageEnglish
Article number3916
JournalNature Communications
Volume5
DOIs
Publication statusPublished - 28 May 2014

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entry
effectors
lumens
Pumps
Inositol 1,4,5-Trisphosphate Receptors
Inositol 1,4,5-Trisphosphate
Membrane Potentials
inositols
pumps
funnels
versatility
cells
Membranes
stems
membranes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

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title = "Mid-range Ca2+ signalling mediated by functional coupling between store-operated Ca2+ entry and IP3-dependent Ca2+ release",
abstract = "The versatility and universality of Ca2+ signals stem from the breadth of their spatial and temporal dynamics. Spatially, Ca2+ signalling is well studied in the microdomain scale, close to a Ca2+ channel, and at the whole-cell level. However, little is known about how local Ca2+ signals are regulated to specifically activate spatially distant effectors without a global Ca2+ rise. Here we show that an intricate coupling between the inositol 1,4,5 trisphosphate (IP3) receptor, SERCA pump and store-operated Ca2+ entry (SOCE) allows for efficient mid-range Ca2+ signalling. Ca2+ flowing through SOCE is taken up into the ER lumen by the SERCA pump, only to be re-released by IP 3Rs to activate distal Ca2+-activated Cl- channels (CaCCs). This CaCC regulation contributes to setting the membrane potential of the cell. Hence functional coupling between SOCE, SERCA and IP 3R limits local Ca2+ diffusion and funnels Ca2+ through the ER lumen to activate a spatially separate Ca2+ effector.",
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N2 - The versatility and universality of Ca2+ signals stem from the breadth of their spatial and temporal dynamics. Spatially, Ca2+ signalling is well studied in the microdomain scale, close to a Ca2+ channel, and at the whole-cell level. However, little is known about how local Ca2+ signals are regulated to specifically activate spatially distant effectors without a global Ca2+ rise. Here we show that an intricate coupling between the inositol 1,4,5 trisphosphate (IP3) receptor, SERCA pump and store-operated Ca2+ entry (SOCE) allows for efficient mid-range Ca2+ signalling. Ca2+ flowing through SOCE is taken up into the ER lumen by the SERCA pump, only to be re-released by IP 3Rs to activate distal Ca2+-activated Cl- channels (CaCCs). This CaCC regulation contributes to setting the membrane potential of the cell. Hence functional coupling between SOCE, SERCA and IP 3R limits local Ca2+ diffusion and funnels Ca2+ through the ER lumen to activate a spatially separate Ca2+ effector.

AB - The versatility and universality of Ca2+ signals stem from the breadth of their spatial and temporal dynamics. Spatially, Ca2+ signalling is well studied in the microdomain scale, close to a Ca2+ channel, and at the whole-cell level. However, little is known about how local Ca2+ signals are regulated to specifically activate spatially distant effectors without a global Ca2+ rise. Here we show that an intricate coupling between the inositol 1,4,5 trisphosphate (IP3) receptor, SERCA pump and store-operated Ca2+ entry (SOCE) allows for efficient mid-range Ca2+ signalling. Ca2+ flowing through SOCE is taken up into the ER lumen by the SERCA pump, only to be re-released by IP 3Rs to activate distal Ca2+-activated Cl- channels (CaCCs). This CaCC regulation contributes to setting the membrane potential of the cell. Hence functional coupling between SOCE, SERCA and IP 3R limits local Ca2+ diffusion and funnels Ca2+ through the ER lumen to activate a spatially separate Ca2+ effector.

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