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Presence of PI-rich vesicles is required for the PLC ζ activation according to mathematical modeling

Phospholipase C ζ (PLCζ) is an enzyme found in the cytoplasm and acrosome of mammalian spermatozoa. It catalyzes the reaction of phosphatidylinositol-4,5-phosphate hydrolysis into inositol-3-phosphate and diacylglycerol. PLCζ is present in the sperm cell acrosome and cytosol but doesn’t significantly affect its metabolism. However, after the fusion of sperm and egg membranes, its activity increases as it begins to bind membranes of the egg. It is unknown why PLCζ is inactive in spermatozoa or any type of somatic cell.

In this work, the modeling approach explains the reasons for the absence of PLCζ activity in any type of mammalian cells but eggs. A model describing the activity of PLCζ in physiological calcium concentrations was developed. It was shown that the presence of phosphoinositide-rich vesicles is required for the PLC ζ activity in mature mammalian eggs.

Scheme of the full model. (A) Reactions in the oocyte, PLCζ – calcium-free PLCζ , PLCζ_Ca – PLCζ, bound with one calcium ion, PLCζ_2Ca – PLCζ, bound with two calcium ions, PLCζ_3Ca  – with three, PLCζ_4Ca  – with four. PLCζ_m  – PLCζ, bound with cell membrane, PLCζ_(Ca m ) – PLCζ, bound with the cell membrane and one calcium ion, PLCζ_(2Ca m )– PLCζ, bound with the cell membrane and two calcium ions, PLCζ_(3Ca m ) – with the cell membrane and three calcium ions, PLCζ_(4Ca m ) – with the cell membrane and four calcium ions. PIP2 and PIP2_v  – are phosphatidylinositol-4,5 – bis-phosphates on cell and vesicle membrane accordingly. DAG and DAG_v  – diacylglycerol on cell membrane and vesicles accordingly. IP3 – inositol-3-phosphate. PLCζ_v – PLCζ, bound with vesicles, PLCζ_(Ca v ) – PLCζ, bound with vesicles and one calcium ion, PLCζ_(2Ca v ) – PLCζ, bound with vesicles and two calcium ions, PLCζ_(3Ca v ) – with vesicles and three calcium ions, PLCζ_(4Ca v ) – with vesicles and four calcium ions. (B) The sperm cell model is identical to the oocyte model except for the absence of the vesicles.
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#phospholipase Cz#calcium signaling#spermatozoa#oocyte

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