Modeling Ca2+ signaling differentiation during oocyte maturation

Ghanim Ullah, Peter Jung, Khaled Machaca

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Ca2+ is a fundamental intracellular signal that mediates a variety of disparate physiological functions often in the same cell. Ca2+ signals span a wide range of spatial and temporal scales, which endow them with the specificity required to induce defined cellular functions. Furthermore, Ca2+ signaling is highly plastic as it is modulated dynamically during normal physiological development and under pathological conditions. However, the molecular mechanisms underlying Ca2+ signaling differentiation during cellular development remain poorly understood. Oocyte maturation in preparation for fertilization provides an exceptionally well-suited model to elucidate Ca2+ signaling regulation during cellular development. This is because a Ca2+ signal with specialized spatial and temporal dynamics is universally essential for egg activation at fertilization. Here we use mathematical modeling to define the critical determinants of Ca2+ signaling differentiation during oocyte maturation. We show that increasing IP3 receptor (IP3R) affinity replicates both elementary and global Ca2+ dynamics observed experimentally following oocyte maturation. Furthermore, our model reveals that because of the Ca2+ dependency of both SERCA and the IP3R, increased IP3R affinity shifts the system's equilibrium to a new steady state of high cytosolic Ca2+, which is essential for fertilization. Therefore our model provides unique insights into how relatively small alterations of the basic molecular mechanisms of Ca2+ signaling components can lead to dramatic alterations in the spatio-temporal properties of Ca2+ dynamics.

Original languageEnglish
Pages (from-to)556-564
Number of pages9
JournalCell Calcium
Volume42
Issue number6
DOIs
Publication statusPublished - 2007
Externally publishedYes

    Fingerprint

Keywords

  • Calcium signaling
  • IP3 receptor
  • Mathematical modeling
  • Oocyte maturation
  • Plasma membrane Ca-ATPase
  • Xenopus

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

Cite this