QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online October 12, 2006
doi: 10.1242/10.1242/dev.02624

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lee, B. Articles by Fissore, R. A. Search for Related Content PubMed PubMed Citation Articles by Lee, B. Articles by Fissore, R. A.

Phosphorylation of IP₃R1 and the regulation of [Ca²⁺]_i responses at fertilization: a role for the MAP kinase pathway

Bora Lee^1,*, Elke Vermassen^2,*,, Sook-Young Yoon¹, Veerle Vanderheyden², Junya Ito¹, Dominique Alfandari¹, Humbert De Smedt², Jan B. Parys² and Rafael A. Fissore^1,

¹ Molecular and Cellular Biology Program and Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01002, USA.
² Laboratorium voor Fysiologie, Katholieke Universiteit Leuven, Campus Gasthuisberg O/N1, bus 802, B-3000 Leuven, Belgium.

Author for correspondence (e-mail: rfissore{at}vasci.umass.edu)

Accepted 31 August 2006

A sperm-induced intracellular Ca²⁺ signal ([Ca²⁺]_i) underlies the initiation of embryo development in most species studied to date. The inositol 1,4,5 trisphosphate receptor type 1 (IP₃R1) in mammals, or its homologue in other species, is thought to mediate the majority of this Ca²⁺ release. IP₃R1-mediated Ca²⁺ release is regulated during oocyte maturation such that it reaches maximal effectiveness at the time of fertilization, which, in mammalian eggs, occurs at the metaphase stage of the second meiosis (MII). Consistent with this, the [Ca²⁺]_i oscillations associated with fertilization in these species occur most prominently during the MII stage. In this study, we have examined the molecular underpinnings of IP₃R1 function in eggs. Using mouse and Xenopus eggs, we show that IP₃R1 is phosphorylated during both maturation and the first cell cycle at a MPM2-detectable epitope(s), which is known to be a target of kinases controlling the cell cycle. In vitro phosphorylation studies reveal that MAPK/ERK2, one of the M-phase kinases, phosphorylates IP₃R1 at at least one highly conserved site, and that its mutation abrogates IP₃R1 phosphorylation in this domain. Our studies also found that activation of the MAPK/ERK pathway is required for the IP₃R1 MPM2 reactivity observed in mouse eggs, and that eggs deprived of the MAPK/ERK pathway during maturation fail to mount normal [Ca²⁺]_i oscillations in response to agonists and show compromised IP₃R1 function. These findings identify IP₃R1 phosphorylation by M-phase kinases as a regulatory mechanism of IP₃R1 function in eggs that serves to optimize [Ca²⁺]_i release at fertilization.

Key words: Fertilization, Ca²⁺, IP3R1, Mouse, MAPK, Xenopus

This article has been cited by other articles:

				M. Levasseur, M. Carroll, K. T. Jones, and A. McDougall A novel mechanism controls the Ca2+ oscillations triggered by activation of ascidian eggs and has an absolute requirement for Cdk1 activity J. Cell Sci., May 15, 2007; 120(10): 1763 - 1771. [Abstract] [Full Text] [PDF]

				R. Ashworth, B. Devogelaere, J. Fabes, R. E. Tunwell, K. R. Koh, H. De Smedt, and S. Patel Molecular and Functional Characterization of Inositol Trisphosphate Receptors during Early Zebrafish Development J. Biol. Chem., May 11, 2007; 282(19): 13984 - 13993. [Abstract] [Full Text] [PDF]