Endoplasmic reticulum remodeling tunes IP3-dependent Ca2+ release sensitivity

Lu Sun, Fang Yu, Aman Ullah, Satanay Zuhair Hubrack, Arwa Daalis, Peter Jung, Khaled Machaca

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The activation of vertebrate development at fertilization relies on IP3-dependent Ca2+ release, a pathway that is sensitized during oocyte maturation. This sensitization has been shown to correlate with the remodeling of the endoplasmic reticulum into large ER patches, however the mechanisms involved are not clear. Here we show that IP3 receptors within ER patches have a higher sensitivity to IP3 than those in the neighboring reticular ER. The lateral diffusion rate of IP3 receptors in both ER domains is similar, and ER patches dynamically fuse with reticular ER, arguing that IP3 receptors exchange freely between the two ER compartments. These results suggest that increasing the density of IP3 receptors through ER remodeling is sufficient to sensitize IP3-dependent Ca2+ release. Mathematical modeling supports this concept of 'geometric sensitization' of IP3 receptors as a population, and argues that it depends on enhanced Ca2+-dependent cooperativity at sub-threshold IP3 concentrations. This represents a novel mechanism of tuning the sensitivity of IP3 receptors through ER remodeling during meiosis.

Original languageEnglish
Article numbere27928
JournalPLoS One
Volume6
Issue number11
DOIs
Publication statusPublished - 30 Nov 2011

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ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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