Endoplasmic Reticulum Remodeling Tunes IP3-Dependent Ca2+ Release Sensitivity

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

doi:10.1371/journal.pone.0027928

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.

Highlights

The egg-to-embryo transition marks the initiation of multicellular organismal development and is instigated by a series of cellular events following fertilization collectively referred to as egg activation [1]
ER remodels during meiosis We have previously shown that elementary IP3-dependent Ca2+
Because ER remodeling was reported to be limited to the vegetal hemisphere of the egg [17], we initially interpreted the clustering of Ca2+ puffs on the animal hemisphere as being due to lateral diffusion of IP3 receptors in the plane of the ER membrane to form overlapping Ca2+ release sites [15]

Summary

Introduction

The egg-to-embryo transition marks the initiation of multicellular organismal development and is instigated by a series of cellular events following fertilization collectively referred to as egg activation [1]. These events are encoded in a sequential fashion by the fertilization-induced Ca2+ transient, which possesses specialized spatial and temporal dynamics that are necessary and sufficient for egg activation [2]. The dynamic remodeling of Ca2+ signaling is fundamental to the developmental competence of the egg [2] It further elegantly illustrates the versatility of Ca2+ signals given the broad bandwidth inherent in their temporal and spatial features. This results in an information rich signal that instructs multiple cellular events at egg activation, including the block to polyspermy and completion of meiosis [2]

Methods

Results

Conclusion