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AuthorNomikos, Michail
AuthorStamatiadis, Panagiotis
AuthorSanders, Jessica R.
AuthorBeck, Konrad
AuthorCalver, Brian L.
AuthorBuntwal, Luke
AuthorLofty, Morgan
AuthorSideratou, Zili
AuthorSwann, Karl
AuthorLai, F. Anthony
Available date2020-11-26T11:21:09Z
Publication Date2017
Publication NameBiochemical Journal
ResourceScopus
URIhttp://dx.doi.org/10.1042/BCJ20161057
URIhttp://hdl.handle.net/10576/17097
AbstractSperm-specific phospholipase C zeta (PLC?) is widely considered to be the physiological stimulus that evokes intracellular calcium (Ca2+) oscillations that are essential for the initiation of egg activation during mammalian fertilisation. A recent genetic study reported a male infertility case that was directly associated with a point mutation in the PLC? C2 domain, where an isoleucine residue had been substituted with a phenylalanine (I489F). Here, we have analysed the effect of this mutation on the in vivo Ca2+ oscillation-inducing activity and the in vitro biochemical properties of human PLC?. Microinjection of cRNA or recombinant protein corresponding to PLC?I489F mutant at physiological concentrations completely failed to cause Ca2+ oscillations and trigger development. However, this infertile phenotype could be effectively rescued by microinjection of relatively high (non-physiological) amounts of recombinant mutant PLC?I489F protein, leading to Ca2+ oscillations and egg activation. Our in vitro biochemical analysis suggested that the PLC?I489F mutant displayed similar enzymatic properties, but dramatically reduced binding to PI(3)P and PI(5)P-containing liposomes compared with wild-type PLC?. Our findings highlight the importance of PLC? at fertilisation and the vital role of the C2 domain in PLC? function, possibly due to its novel binding characteristics.
Languageen
PublisherPortland Press Ltd
TitleMale infertility-linked point mutation reveals a vital binding role for the C2 domain of sperm PLC?
TypeArticle
Pagination1003-1016
Issue Number6
Volume Number474
dc.accessType Abstract Only


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