Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Male infertility-linked point mutation reveals a vital binding role for the C2 domain of sperm PLCζ

Nomikos, Michail, Stamatiadis, Panagiotis, Sanders, Jessica Rose, Beck, Konrad ORCID: https://orcid.org/0000-0001-5098-9484, Calver, Brian Lewis, Buntwal, Luke, Lofty, Morgan, Sideratou, Zili, Swann, Karl ORCID: https://orcid.org/0000-0002-4355-1449 and Lai, Francis Anthony ORCID: https://orcid.org/0000-0003-2852-8547 2017. Male infertility-linked point mutation reveals a vital binding role for the C2 domain of sperm PLCζ. Biochemical Journal 474 (6) , pp. 1003-1016. 10.1042/BCJ20161057

[thumbnail of BJ Post print manuscript (word  doc) (002).pdf]
Preview
PDF - Accepted Post-Print Version
Download (1MB) | Preview

Abstract

Sperm-specific phospholipase C zeta (PLCζ) 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 PLCζ 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 PLCζ. Microinjection of cRNA or recombinant protein corresponding to PLCζI489F 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 PLCζI489F protein, leading to Ca2+ oscillations and egg activation. Our in vitro biochemical analysis suggested that the PLCζI489F mutant displayed similar enzymatic properties, but dramatically reduced binding to PI(3)P and PI(5)P-containing liposomes compared with wild-type PLCζ. Our findings highlight the importance of PLCζ at fertilisation and the vital role of the C2 domain in PLCζ function, possibly due to its novel binding characteristics.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Dentistry
Uncontrolled Keywords: Male infertility, Fertilization, Sperm, Phospholipase C zeta (PLC), calcium oscillations, C2 domain
Publisher: Biochemical Society
ISSN: 0264-6021
Date of First Compliant Deposit: 25 May 2017
Date of Acceptance: 20 January 2017
Last Modified: 28 Mar 2024 16:40
URI: https://orca.cardiff.ac.uk/id/eprint/100874

Citation Data

Cited 20 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics