Modeling Ca2+ signaling differentiation during oocyte maturation.
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.
Ullah
Ghanim
G
Department of Physics and Astronomy and Quantitative Biology Institute, Ohio University, Athens, OH 45701, USA.
Jung
Peter
P
Machaca
Khaled
K
D000465:Algorithms; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D005260:Female; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000502:physiology; D008954:Models, Biological; D009865:Oocytes / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000378:metabolism; D014981:Xenopus
D053496:Inositol 1,4,5-Trisphosphate Receptors; D053499:Plasma Membrane Calcium-Transporting ATPases; D002118:Calcium