4.6 Article

Human PLCζ exhibits superior fertilization potency over mouse PLCζ in triggering the Ca2+ oscillations required for mammalian oocyte activation

Journal

MOLECULAR HUMAN REPRODUCTION
Volume 20, Issue 6, Pages 489-498

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/molehr/gau011

Keywords

phospholipase C; PLCzeta; sperm; fertilization; oocyte activation; male infertility

Funding

  1. Wellcome Trust [080701]
  2. Libyan Government
  3. NCSR Demokritos

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A sperm-specific phospholipase C-zeta (PLC zeta) is believed to play an essential role in oocyte activation during mammalian fertilization. Sperm PLC zeta has been shown to trigger a prolonged series of repetitive Ca2+ transients or oscillations in oocytes that precede activation. This remarkable intracellular Ca2+ signalling phenomenon is a distinctive characteristic observed during in vitro fertilization by sperm. Previous studies have notably observed an apparent differential ability of PLC zeta from disparate mammalian species to trigger Ca2+ oscillations in mouse oocytes. However, the molecular basis and confirmation of the apparent PLC zeta species difference in activity remains to be provided. In the present study, we provide direct evidence for the superior effectiveness of human PLC zeta relative to mouse PLC zeta in generating Ca2+ oscillations in mouse oocytes. In addition, we have designed and constructed a series of human/mouse PLC zeta chimeras to enable study of the potential role of discrete PLC zeta domains in conferring the enhanced Ca2+ signalling potency of human PLC zeta. Functional analysis of these human/mouse PLC zeta domain chimeras suggests a novel role of the EF-hand domain in the species-specific differences in PLC zeta activity. Our empirical observations are compatible with a basic mathematical model for the Ca2+ dependence of generating cytoplasmic Ca2+ oscillations in mammalian oocytes by sperm PLC zeta.

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