Recombinant Human 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase zeta-1 (PLCZ1)

Function

The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. In vitro, hydrolyzes PtdIns(4,5)P2 in a Ca(2+)-dependent manner. Triggers intracellular Ca(2+) oscillations in oocytes solely during M phase and is involved in inducing oocyte activation and initiating embryonic development up to the blastocyst stage. Is therefore a strong candidate for the egg-activating soluble sperm factor that is transferred from the sperm into the egg cytoplasm following gamete membrane fusion. May exert an inhibitory effect on phospholipase-C-coupled processes that depend on calcium ions and protein kinase C, including CFTR trafficking and function

Subcellular Location

Nucleus; Cytoplasm, perinuclear region; Cytoplasmic vesicle, secretory vesicle, acrosome

Disease Association

Spermatogenic failure 17 (SPGF17) : An autosomal recessive infertility disorder due to failure of oocyte activation and fertilization by sperm that otherwise exhibits normal morphology. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Expressed specifically in testis and sperm. Weakly expressed in pancreatic-duct cells. Up-regulated in pancreatic-duct cells from patients with cystic fibrosis

Subunit

Interacts via its C2 domain with PtdIns(3)P and, to a lesser extent, PtdIns(5)P in vitro

• Cox L.J. et al. Sperm phospholipase Czeta from humans and cynomolgus monkeys triggers Ca2+ oscillations, activation and development of mouse oocytes. — Reproduction (2002)
• Zhu H. et al. Rescue of defective pancreatic secretion in cystic-fibrosis cells by suppression of a novel isoform of phospholipase C. — Lancet (2003)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Rogers N.T. et al. Phospholipase Czeta causes Ca2+ oscillations and parthenogenetic activation of human oocytes. — Reproduction (2004)
• Escoffier J. et al. Homozygous mutation of PLCZ1 leads to defective human oocyte activation and infertility that is not rescued by the WW-binding protein PAWP. — Hum. Mol. Genet. (2016)
• Zhao S. et al. Novel variants in ACTL7A and PLCZ1 are associated with male infertility and total fertilization failure. — Clin. Genet. (2023)
• Hua R. et al. ACROSIN deficiency causes total fertilization failure in humans by preventing the sperm from penetrating the zona pellucida. — Hum. Reprod. (2023)